Somatic Mutations in Cancer | Genetic Sequencing

Luminus Diagnostics’ somatic cancer diagnostics testing leverages proven technology and provide a noninvasive and cost-effective solution for high-sensitivity monitoring across a variety of sample types.

Our unique technology uses minimal volumes of blood to provide unprecedented tumor monitoring information with an up-to-date clinical status in a more complete, accurate, timely, less expensive and less invasive fashion.

HIGHLIGHTS & CREDENTIALS

  • Clinically validated assays
  • Unprecedented levels of cell-free DNA recovery from droplet volumes of blood translates into high sensitivity
  • Open platforms, Ion Torrent Proton for both mutation monitoring and profiling
  • Integrated workflow for consistent and reliable longitudinal studies

CLINICAL CHALLENGES

Individualized cancer management for treating cancer patients with precision therapy is currently still challenged by the following limitations:

Tumor heterogeneity: tumors are heterogeneous and exhibit continuously polyclonal expansion, thus complicating diagnosis, treatment and the assessment of acquired resistance. Furthermore, tumor tissues are limited both spatially to the region biopsied and temporally to the state of tumor at the time of biopsy.

Accessibility of tumor tissue: the majority of patients treated with targeted therapies ultimately develop resistance, metastasis or recurrence. Effective monitoring with several tumor samples is not clinically practical with current, invasive biopsy techniques. Most importantly, tumor tissue may not be available or has been exhausted due to multiple testings.


Unmet Needs in Liquid Biopsy

Novel cell-free DNA enrichment method for high-quantity and high-quality starting materials:

Circulating, cell-free DNA is highly fragmented and presented at very low concentrations. This makes its isolation challenging due to the requirements of high-volume input, costs and labor intensity. Our proprietary cell-free DNA enrichment process possesses the novel characteristic of low input (as low as 50 uL of plasma) and high output (>300 ng/mL), allowing ultra-high recovery and detection of tumor DNA directly from droplet volumes of unprocessed blood.

Advanced NGS technology for sensitive longitudinal mutation detection:
Detection of low-frequency mutations through periodic cell-free DNA analysis could predict tumor progression before the lesions are large enough to be detected by imaging. Analysis beyond a single mutation could also be warranted to capture tumor heterogeneity for effective treatment decision making. Liquid biopsies are not as spatially limited as tissue biopsies and can show a global spectrum of mutations that occur throughout tumor development in our body. The sensitivity of conventional analytical methods such as Sanger sequencing is not sufficient to detect low-frequency variants. Targeted deep sequencing by next-generation sequencing (NGS) provides a cost-effective alternative for high-throughput analysis of multiple mutations with high sensitivity.

Validated sample processing and analysis procedure in clinical practice:
The utility of cell-free DNA for clinical application demands the implementation of stringent pre-analytical validation of our laboratory developed tests to ensure consistent quality data acquisition in our CLIA-certified laboratory.

KEY METRICS

  • Regions Analyzed: Mutation hotspot regions of 50 cancer-associated genes
  • Sequencing Method: Ion Proton NGS
  • Assay Sensitivity: >1.0%
  • Target Sequencing Coverage: 5,000x
  • Turnaround Time: 5-7 days
  • Sample Requirements: Finger stick, blood/microcontainer, purple top EDTA 250-500 uL tube
  • Sample Types: Plasma or Serum
  • Sample Input Required: Droplet Volumes (50-500 uL)

SAMPLE QUALITY AND QUANTITY

Our proven method provides a simple, streamlined, and robust workflow optimized for cell-free DNA enrichment/recovery from a droplet of plasma or serum as an alternative to low-quantity, poor-quality DNA from challenging tissue biopsy samples. This sample preparation breakthrough enables multiple analyses on a droplet sample by a broad range of genomic platforms, including (NGS), microarrays, quantitative PCR (qPCR) and droplet digital PCR (ddPCR). Working with challenging and precious samples is no longer a barrier to personalized cancer therapy. Our technology allows us to work with a sample volume as small as 50 uL, saving the remainder of your biobank for other clinical testing.

We compared the sensitivity of our proprietary cell-free DNA enrichment method to the standard DNA extraction kit used industry wide today. Results demonstrated 100x more cell-free tumor DNA in the original sample using a single drop of blood.

SAMPLE COLLECTION

Large sample volume, low yield and labor intensiveness are the major barriers to the routine use of cell-free DNA-based testing in current clinical settings. Specifically, cell-free DNA recovery efficiency using the current standard silica membrane/bead method is extremely low due to unavoidable loss in steps such as binding, washing and elution. This in turn results in a minimum sample requirement of 5-10mL of blood.

While almost all liquid biopsy providers are working and perfecting their novel technologies to selectively enrich or amplify tumor specific, cell-free DNA from a dominantly normal population, their starting materials are still those “incomplete” DNA molecules that survived after extraction/isolation. As a result, no matter how sensitive their technology is (downstream), they cannot detect cell-free DNA already lost during sample preparation (upstream). Further, there is uncertainty if even 10 mL of blood is enough.

In contrast, Luminus focuses on the first step in the cell-free DNA process, making sure we capture all of the cell-free DNA molecules existing in the original sample. Our breakthrough, proprietary method enables recovery of both necrotic and apoptotic cell-death-associated, cell-free DNA, with a high-yield, high-degree genomic representation and high sequencing quality.

SENSITIVITY + ACCURACY

Luminus’ cell-free DNA enrichment process is a complete solution for generations of high-yield, high-quality, well-represented tumor DNA from droplet amounts of plasma or serum. It is the first non-invasive method that allows accurate NGS genomic analyses directly from droplet volumes of blood. Our protocol can be applied to a broad range of clinical genetic tests with the advantages of minimal sample volume, maximal yield and streamlined workflow with reduced cost and turnaround time.

AUTOMATION

Luminus’ automated solutions have been developed to establish a complete and efficient NGS workflow from sample-in to report-out. The simplicity and robustness of our automated process enables interfaces and cross-talks between a variety of platforms and laboratory information management systems. Using this simplified workflow, an automated workstation can easily process 96 or more samples at one time.

SOMATIC CANCER | A CLOSER LOOK


SOMATIC CANCER | HIGHLIGHTED TESTS


MSI | Microsatellite instability

Microsatellite instability (MSI) is a well-recognized phenomenon that is classically a feature of tumors in the hereditary non-polyposis colorectal syndrome. Ten to 15% of sporadic colorectal cancers, however, will have MSI. Microsatellite unstable tumors can be divided into two distinct MSI phenotypes: MSI-high (MSI-H) and MSI-low (MSI-L). MSI sporadic colorectal cancers with a high level of MSI (MSI-H) form a well-defined group with distinct clinicopathologic features characterized by an overall better long-term prognosis. These sporadic MSI-H colorectal tumors most often arise from the epigenetic silencing of the mismatch repair gene MLH1. In contrast, MSI-L colorectal tumors have not been shown to differ in their clinicopathologic features or in most molecular features from microsatellite stable (MSS) tumors. Unlike MSI-H tumors, MSI-L tumors appear to arise through the chromosomal instability carcinogenesis pathway, similar to MSS tumors. Some groups have reported more frequent mutations in K-ras and in the methylation of methylguanine transferase in MSI-L tumors, but others have questioned these findings. Therefore, although the use of the MSI-L category is widespread, there continues to be some debate as to whether a discrete MSI-L group truly exists. Rather, it has been suggested that MSI-L tumors differ quantitatively from MSS tumors but do not differ qualitatively. Future studies will need to evaluate the specific mutations in non-MSI-H tumors in an attempt to sub-classify MSI-L tumors with regard to MSS tumors so that subtle differences between these two sub-groups can be identified. (1)

The U.S. Food and Drug Administration granted accelerated approval to Keytruda (pembrolizumab) for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This indication covers patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and patients with colorectal cancer that has progressed following treatment with certain chemotherapy drugs. MSI-H and dMMR tumors contain abnormalities that affect the proper repair of DNA inside the cell.

Tumors with these biomarkers are most commonly found in colorectal, endometrial and gastrointestinal cancers, but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland and other places. Approximately 5 percent of patients with metastatic colorectal cancer have MSI-H or dMMR tumors. Keytruda works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, Keytruda may help the body’s immune system fight the cancer cells. (2)

1. Dis Markers. 2004;20(4-5):199-206. Colorectal carcinogenesis: MSI-H versus MSI-L. Pawlik TM 1 , Raut CP, Rodriguez-Bigas MA. Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

2. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm560167.htm

NTRK | Neurotrophic tropomyosin receptor kinase

NTRK (Neurotrophic tropomyosin receptor kinase)

The tropomyosin receptor kinase (Trk) receptor family comprises 3 transmembrane proteins referred to as Trk A, B and C (TrkA, TrkB and TrkC) receptors that are encoded by the NTRK1, NTRK2 and NTRK3 genes, respectively.  Gene fusions involving NTRK genes lead to transcription of chimeric Trk proteins with constitutively activated or overexpressed kinase function conferring oncogenic potential. (1)

The latter are specific ligands known as nerve growth factor (NGF) for TrkA, brain-derived growth factor (BDGF), and NT-4/5 for TrkB and NT3 for TrkC, respectively. (2) The binding of the ligand to the receptor triggers the oligomerisation of the receptors and phosphorylation of specific tyrosine residues in the intracytoplasmic kinase domain. This event results into the activation of signal transduction pathways leading to proliferation, differentiation and survival in normal and neoplastic neuronal cells. The binding of TrkA receptor by NGF causes the activation of the Ras/Mitogen activated protein kinase (MAPK) pathway, which leads to increased proliferation and cellular growth through extracellular signal-regulated kinase (ERK) signalling. Other pathways such as phospholipase C-γ (PLCγ) and PI3K are also activated. TrkC coupling with NT3 causes preferential activation of the PI3/AKT pathway preventing apoptosis and increasing cell survival, whereas TrkB transduces the BDNF signal via Ras-ERK, PI3K and PLCγ pathway, resulting in neuronal differentiation and survival.

Colorectal Adenocarcinoma
In 2015, Créancier et al (3) reported the 0.5% prevalence of NTRK fusions in 408 CRC clinical samples, including a TPM3-NTRK1 (TRK-T2 fusion).  Braghiroli et al (4) reported a 4% (2 of the 49 cases) of incidence of NTRK unidentified fusions in appendiceal adenocarcinoma.

Lung Adenocarcinoma
In 2013, Vaishnavi et al (5) described two different gene fusions involving the NTRK1 gene that lead to constitutive TrkA TK domain activation.  A total of 3.3% patients in this study (3/91) harboured NTRK rearrangements potentially susceptible to TrkA inhibitors.

Papillary Thyroid Carcinoma
Bongarzone et al (6) in 1989 described an oncogenic version of NTRK1 in PTC. TRK-T1 and TRK-T2 are two different hybrid forms derived from chromosome inversion and different portions of TPR (Translocated Promoter Region) gene on chromosome 1q25 activate them. Another NTRK1 oncogene obtained by fusion with the TFG gene (TRK fused gene) on chromosome 3 is TRK–T3, all of which are oncogenic. Somatic rearrangements of the NTRK1 gene in PTC usually do not exceed 12%, but range quite widely across different populations (from 15% to 50% in the Italian population (6), to <10% in French (7), Japanese (8), and Chinese (9)).

Human secretory breast carcinoma

This is a rare but distinct subtype of infiltrating ductal carcinoma that was originally described in children and adolescents, but is now known to occur with equal incidence in adults. In 2002, Tognon et al (10) reported the ETV6-NTRK3 gene fusion t(12;15)(p12;q26.1) as a pathognomonic genetic feature of this rare carcinoma.

Glioblastoma

Gene fusions occur in approximately 30–50% of patient with glioblastoma (GBM) samples and the Trk family could play a very important role. In 2014, Wu et al (11) applied a whole genome, whole exome and/or transcriptome sequencing to 127 samples of pediatric high-grade glioma (HGG), identifying recurrent fusions involving the neurotrophin receptor genes NTRK1, 2, or 3 in 40% of non-brainstem HGG.

Miscellaneous tumors

The recent efforts for identifying targetable genomic alterations through the use of next generation sequencing (NGS) are leading to the identification of novel and recurrent gene fusions in other various types of cancer. Ross et al (12) reported a NGS screening of 28 FFPE samples of intrahepatic cholangiocarcinoma, in which a novel gene fusion RABGAP1L-NTRK1 was identified from a liver biopsy of a 62-year-old woman. Further, a recurrent gene fusion involving the ETV6 and the NTRK3 gene (ETV6-NTRK3) has been described in congenital fibrosarcoma (13).

TRK Inhibitors

Entrectinib, formerly RXDX-101 and NMS-E628, is an orally bioavailable inhibitor of the TK TrkA, TrkB and TrkC, as well as of C-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK). Entrectinib can cross the blood–brain barrier, and could thus potentially be effective in the treatment of brain metastases and GBM by activating gene fusions of NTRK, ROS1 or ALK. As with other targeted therapies, the onset of acquired (secondary) resistance may limit the efficacy of Trk inhibitors. Given their recent introduction into the therapeutic armamentarium of cancer treatment, very limited data are available regarding mechanisms underlying resistance. Recently, a study by Russo et alunveiled gene alterations associated with entrectinib-acquired resistance.

  1. Nakagawara A. Trk receptor tyrosine kinases: a bridge between cancer and neural development. Cancer Lett 2001;169:107–14. 
  2. Huang EJ, Reichardt LF. Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem2003;72:609–42.
  3. Créancier L, Vandenberghe I, Gomes B, et al. Chromosomal rearrangements involving the NTRK1 gene in colorectal carcinoma. Cancer Lett 2015;365:107–11.
  4. Braghiroli MI, Genomic profiling and efficacy of anti-EGFR therapy in appendiceal adenocarcinoma. J Clin Oncol 2016;34(Suppl 4S):abstr 574.
  5. Vaishnavi A, Capelletti M, Le AT, et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med 2013;19:1469–72. 
  6. Bongarzone I, Pierotti MA, Monzini N, et al. High frequency of activation of tyrosine kinase oncogenes in human papillary thyroid carcinoma. Oncogene 1989;4:1457–62.
  7. Bongarzone I, Pierotti MA, Monzini N, et al. High frequency of activation of tyrosine kinase oncogenes in human papillary thyroid carcinoma. Oncogene 1989;4:1457–62.
  8. Bongarzone I, Pierotti MA, Monzini N, et al. High frequency of activation of tyrosine kinase oncogenes in human papillary thyroid carcinoma. Oncogene 1989;4:1457–62.
  9. Bongarzone I, Pierotti MA, Monzini N, et al. High frequency of activation of tyrosine kinase oncogenes in human papillary thyroid carcinoma. Oncogene 1989;4:1457–62.

      10. Tognon C, Knezevich SR, Huntsman D, et al. Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell 2002;2:367–76

  1. Wu G, Diaz AK, Paugh BS, et al. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 2014;46:444–50.
  2. Ross JS, Wang K, Gay L, et al. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncologist 2014;19:235–42. 

13. Knezevich SR, McFadden DE, Tao W, et al. A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet 1998;18:184–7.

PDL-1 | Programmed death ligand -1

Programmed death ligand -1 (PDL-1) Expression of PD-L1 is an important variable when analyzing results of therapy with anti–PD-1/L1 antibodies for cancer. PD-L1 positivity is only desirable in the context of treatment targeting the PD-1–PD-L1 interaction, as in the absence of this therapy it may be a mechanism of immune escape that is only beneficial to the cancer cells. In the future, it is likely that rational decisions on the use of anti–PD-1/L1 antibody therapy alone or in combination will be based on the assessment of the presence or absence of tumor antigen–specific T cells that are inhibited by PD-L1 expression by cancer cells. (1)

Immunotherapy with anti–programmed death-1 (PD-1) or anti–PD-1 ligand 1 (PD-L1) antibodies has been approved for the treatment of several cancers because of impressive durable responses. Opdivo (nivolumab), has been approveds to treat certain patients with squamous non-small-cell lung cancer (NSCLC), and can also provide significant benefit to patients with the more common nonsquamous form of NSCLC, especially those with tumors expressing high levels of tumor programmed death-ligand 1 (PD-L1), according to findings from the phase III CheckMate-057 study.

Lung cancer is the leading cause of cancer death in the U.S., with an estimated 224,210 new diagnoses and 159,260 deaths in 2014. The most common type of lung cancer, NSCLC affects seven out of eight lung cancer patients, occurring when cancer forms in the cells of the lung.

The 582-patient study is the first to demonstrate that a PD-1 inhibitor significantly improves overall survival vs. docetaxel in previously treated patients with nonsquamous NSCLC. It also highlighted the role of PD-L1 expression in the disease, demonstrating that patients with high levels of PD-L1 in their tumors (>/= 1 percent of tumor cells) had a doubling of median overall survival at 17 months to 19 months, compared with standard-of-care docetaxel, at eight to nine months. PD-L1 expression seems to be a predictive factor for the benefit of nivolumab treatment. (2)

1. Ribas, A., & Hu-Lieskovan, S. (2016). What does PD-L1 positive or negative mean?. The Journal of experimental medicine, 213(13), 2835-2840.

2. Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in advanced non-squamous cell (non-SQ) non-small cell lung cancer (NSCLC). Luis Paz Ares, Leora Horn, Hossein Borghaei, David R. Spigel, Martin Steins, Neal Ready, Laura Quan Man Chow, Everett E. Vokes, Enriqueta Felip, Esther Holgado, Fabrice Barlesi, Martin Kohlhaeufl, Oscar Rodriguez, Marco Angelo Burgio, Jerome Fayette, Scott N. Gettinger, Christopher Harbison, Cécile Dorange, Friedrich Graf Finckenstein, and Julie R. Brahmer Journal of Clinical Oncology 2015 33:18_suppl, LBA109-LBA109

SOMATIC CANCER | SAMPLE PATIENT REPORT


SOMATIC CANCER | PROFILES AVAILABLE


LUMINUS BLADDER | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: TP53, PTEN, RB1, PIK3CA

LUMINUS BREAST | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: PIK3CA, ERBB2, AKT1, PTEN

LUMINUS COLORECTAL | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: BRAF, NRAS, PIK3CA, KRAS

LUMINUS COMPREHENSIVE LUNG PANEL | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: EGFR, KRAS, ALK, PIK3CA, BRAF, ALK Gene Fusion (RNA), ROS1 Gene Fusion (RNA), PD-L1 Expression

LUMINUS GALLBLADDER | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: TP53, PIK3CA, KRAS, BRAF

LUMINUS GASTRIC | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: APC, KRAS, BRAF, PIK3CA

LUMINUS GIST | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: KIT, PDGFRA, BRAF

LUMINUS HEAD & NECK | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: TP53, PIK3CA, NOTCH1, CDKN2A

LUMINUS HEMATOLOGICAL | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: FLT3, NPM1, JAK2, ABL1

LUMINUS IMMUNOTHERAPY | SOMATIC CANCER PANEL

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: MSI-H, PD-L1 Expression

LUMINUS LIQUID BIOPSY | SOMATIC CANCER PROFILE

SPECIMEN: 5 ML WHOLE-BLOOD

TUBE TYPE: LAVENDER-TOP TUBE

MINIMUM VOLUME: 5 ML

PURPOSE: FOR PRE + POST TREATMENTS AND LONGITUDINAL RESPONSE STUDIES

THIS PANEL INCLUDES: ABL1, AKT1, ALK, ALK Gene Fusion (RNA), APC, BRAF, CDKN2A, EGFR, ERBB2, FLT3, JAK2, JAK3, KIT, KRAS, MSI-H, NOTCH1, NRAS, NPM1, PDGFRA, PD-L1 Expression, PIK3CA, PTEN, RB1, RET, ROS1 Gene Fusion (RNA), TP53

LUMINUS MELANOMA | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: BRAF, NRAS, KIT

LUMINUS OVARIAN | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: KRAS, BRAF, PIK3CA, PTEN

LUMINUS PANCREATIC | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: KRAS, CDKN2A, TP53

LUMINUS PROSTATE | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: TP53, PTEN, KRAS, PIK3CA

LUMINUS THYROID | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: KRAS, BRAF, RET, NRAS

LUMINUS RNA TEST | SOMATIC CANCER PROFILE

SPECIMEN: SOMATIC TISSUE

CONTAINER TYPE: SEE TRANSPORT

VOLUME: SEE TRANSPORT

TRANSPORT:

  • OPTION 1:
    A FORMALIN FIXED, PARAFFIN EMBEDDED (FFPE) BLOCK
    CONTAINING THE PATIENT’S TUMOR TISSUE.
    (PLEASE INCLUDE ADDRESS FOR RETURNING THE BLOCK.)OR
  • OPTION 2:
    ONE H&E STAINED 10 MICRON SLIDE
    – IF ORDERING MSI, 20% OF SAMPLE MUST BE NORMAL CELLS
    FIVE UNBAKED, UNSTAINED, 10 MICRON SECTIONS ON
    POSITIVELY CHARGED GLASS SLIDES.
    (FOR SMALL BIOPSIES WHERE TOTAL TISSUE IS LESS THAN
    5MM X 5MM, PLACE TWO SECTIONS ON EACH SLIDE.)

    • AIR DRY – DO NOT OVEN DRY
    • DO NOT USE COVER-SLIPS
  • OPTION 3:
    LAVENDER-TOP (EDTA) TUBE

THIS PANEL INCLUDES: ALK Gene Fusion, ROS1 Gene Fusion

FDA Approved Targeted Therapies | Genetic Therapies


CLICK TO VIEW FDA APPROVED TARGETED THERAPIES

ABL1
Bosutinib
Busulfan
Dasatinib
Imatinib
Nilotinib
Omacetaxine
Ponatinib
ALK
Ceritinib
Crizotinib
BRAF
Dabrafenib
Trametinib
Vemurafenib
EGFR
Afatinib
Cetuximab
Erlotinib
Gefitinib
Lapatinib
Panitumumab
Vandetanib
ERBB2
Ado-Trastuzumab
Emtansine
Everolimus
Lapatinib
Pertuzumab
Trastuzumab
FLT3
Cabozantinib
Ponatinib
JAK2
Ruxolitinib
JAK3
Tofacitinib
KIT
Axitinib
Cabozantinib
Imatinib
Pazopanib
Regorafenib
Sorafenib
KRAS
Cetuximab
Panitumumab
MET
Cabozantinib
Crizotinib
PDGFRA
Axitinib
Imatinib
Pazopanib
Sorafenib
RET
Cabozantinib
Regorafenib
Vandetanib
ALK GENE FUSION
Alectinib
Brigatinib
Crizotinib
Ceritinib
ROS1 GENE FUSION
Crizotinib
PD-L1 EXPRESSION
Pembrolizumab
Nivolumab
MSI-H
Pembrolizumab
Nivolumab

Somatic Mutations in Cancer | Gene Panels


CLICK TO VIEW OUR SOMATIC PANELS

Luminus Colorectal
BRAF
NRAS
PIK3CA
KRAS
Luminus Gastric
APC
KRAS
BRAF
PIK3CA
Luminus Prostate
TP53
PTEN
KRAS
PIK3CA
Luminus GIST
KIT
PDGFRA
BRAF
Luminus Hematological
FLT3
NPM1
JAK2
ABL1
Luminus Head and Neck
TP53
PIK3CA
NOTCH1
CDKN2A
Luminus Breast
PIK3CA
ERBB2
AKT1
PTEN
Luminus Ovarian
KRAS
BRAF
PIK3CA
PTEN
Luminus Thyroid
KRAS
BRAF
RET
NRAS
Luminus Gallbladder
TP53
PIK3CA
KRAS
BRAF
Luminus Melanoma
BRAF
NRAS
KIT
Luminus Pancreatic
KRAS
CDKN2A
TP53
Luminus Bladder
TP53
PTEN
RB1
PIK3CA
Comprehensive Lung Panel
EGFR
KRAS
ALK
PIK3CA
BRAF
ALK Gene Fusion (RNA)
ROS1 Gene Fusion (RNA)
PD-L1 Expression
RNA TEST MENU
ALK Gene Fusion
ROS1 Gene Fusion
IMMUNOTHERAPY
MSI-H
PD-L1 Expression
LIQUID BIOPSY


ABL1 AKT1 ALK ALK Gene Fusion (RNA)
APC BRAF CDKN2A EGFR
ERBB2 FLT3 JAK2 JAK3
KIT KRAS MSI-H NOTCH1
NRAS NPM1 PDGFRA PD-L1 Expression
PIK3CA PTEN RB1 RET
ROS1 Gene Fusion (RNA) TP53

Somatic Mutations in Cancer | Gene Descriptions

ABL1

This gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5′ end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014]

AKT1

The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Mutations in this gene have been associated with the Proteus syndrome. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2011]

ALK

This gene encodes a receptor tyrosine kinase, which belongs to the insulin receptor superfamily. This protein comprises an extracellular domain, an hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. It plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. This gene has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. The chromosomal rearrangements are the most common genetic alterations in this gene, which result in creation of multiple fusion genes in tumourigenesis, including ALK (chromosome 2)/EML4 (chromosome 2), ALK/RANBP2 (chromosome 2), ALK/ATIC (chromosome 2), ALK/TFG (chromosome 3), ALK/NPM1
(chromosome 5), ALK/SQSTM1 (chromosome 5), ALK/KIF5B (chromosome 10), ALK/CLTC (chromosome 17), ALK/TPM4 (chromosome 19), and ALK/MSN (chromosome X).[provided by RefSeq, Jan 2011]

APC

This gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It is also involved in other processes including cell migration and adhesion, transcriptional activation, and apoptosis. Defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. [provided by RefSeq, Jul 2008]

ATM

The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]

BRAF

This gene encodes a protein belonging to the RAF family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERK signaling pathway, which affects cell division, differentiation, and secretion. Mutations in this gene, most commonly the V600E mutation, are the most frequently identified cancer-causing mutations in melanoma, and have been identified in various other cancers as well, including non-Hodgkin lymphoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia and adenocarcinoma of lung. Mutations in this gene are also associated with cardiofaciocutaneous, Noonan, and Costello syndromes, which exhibit overlapping phenotypes. A pseudogene of this gene has been identified on the X chromosome. [provided by RefSeq, Aug 2017]

CDH1

This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function of this gene is thought to contribute to cancer progression by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. This gene is present in a gene cluster with other members of the cadherin family on chromosome 16. [provided by RefSeq, Nov 2015]

CDKN2A

This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. [provided by RefSeq, Sep 2012]

CSF1R

The protein encoded by this gene is the receptor for colony stimulating factor 1, a cytokine which controls the production, differentiation, and function of macrophages. This receptor mediates most if not all of the biological effects of this cytokine. Ligand binding activates the receptor kinase through a process of oligomerization and transphosphorylation. The encoded protein is a tyrosine kinase transmembrane receptor and member of the CSF1/PDGF receptor family of tyrosine-protein kinases. Mutations in this gene have been associated with a predisposition to myeloid malignancy. The first intron of this gene contains a transcriptionally inactive ribosomal protein L7 processed pseudogene oriented in the opposite direction. Alternative splicing results in multiple transcript variants. Expression of a splice variant from an LTR promoter has been found in Hodgkin lymphoma (HL), HL cell lines and anaplastic large cell lymphoma. [provided by RefSeq, Mar 2017]

CTNNB1

The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Mutations in this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

EGFR

The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. [provided by RefSeq, Jun 2016]

ERBB2

This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]

ERBB4

This gene is a member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. It encodes a single-pass type I membrane protein with multiple cysteine rich domains, a transmembrane domain, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins and other factors and induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

EZH2

This gene encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein associates with the embryonic ectoderm development protein, the VAV1 oncoprotein, and the X-linked nuclear protein. This protein may play a role in the hematopoietic and central nervous systems. Multiple alternatively splcied transcript variants encoding distinct isoforms have been identified for this gene.
[provided by RefSeq, Feb 2011]

FBXW7

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene was previously referred to as FBX30, and belongs to the Fbws class; in addition to an F-box, this protein contains 7 tandem WD40 repeats. This protein binds directly to cyclin E and probably targets cyclin E for ubiquitin-mediated degradation. Mutations in this gene are detected in ovarian and breast cancer cell lines, implicating the gene’s potential role in the pathogenesis of human cancers. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

FGFR1

The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

FGFR2

The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member is a high-affinity receptor for acidic, basic and/or keratinocyte growth factor, depending on the isoform. Mutations in this gene are associated with Crouzon syndrome, Pfeiffer syndrome, Craniosynostosis, Apert syndrome, Jackson-Weiss syndrome, Beare-Stevenson cutis gyrata syndrome, Saethre-Chotzen syndrome, and syndromic craniosynostosis. Multiple alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009]

FGFR3

This gene encodes a member of the fibroblast growth factor receptor (FGFR) family, with its amino acid sequence being highly conserved between members and among divergent species. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds acidic and basic fibroblast growth hormone and plays a role in bone development and maintenance. Mutations in this gene lead to craniosynostosis and multiple types of skeletal dysplasia. [provided by RefSeq, Aug 2017]

FLT3

This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia.
[provided by RefSeq, Jan 2015]

GNA11

The protein encoded by this gene belongs to the family of guanine nucleotide-binding proteins (G proteins), which function as modulators or transducers in various transmembrane signaling systems. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes one of the alpha subunits (subunit alpha-11). Mutations in this gene have been associated with hypocalciuric hypercalcemia type II (HHC2) and hypocalcemia dominant 2 (HYPOC2). Patients with HHC2 and HYPOC2 exhibit decreased or increased sensitivity, respectively, to changes in extracellular calcium concentrations. [provided by RefSeq, Dec 2013]

GNAQ

This locus encodes a guanine nucleotide-binding protein. The encoded protein, an alpha subunit in the Gq class, couples a seven-transmembrane domain receptor to activation of phospolipase C-beta. Mutations at this locus have been associated with problems in platelet activation and aggregation. A related pseudogene exists on chromosome 2.[provided by RefSeq, Nov 2010]

GNAS

This locus has a highly complex imprinted expression pattern. It gives rise to maternally, paternally, and biallelically expressed transcripts that are derived from four alternative promoters and 5′ exons. Some transcripts contain a differentially methylated region (DMR) at their 5′ exons, and this DMR is commonly found in imprinted genes and correlates with transcript expression. An antisense transcript is produced from an overlapping locus on the opposite strand. One of the transcripts produced from this locus, and the antisense transcript, are paternally expressed noncoding RNAs, and may regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping ORF, which encodes a structurally unrelated protein – Alex. Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit, a key element of the classical signal transduction pathway linking receptor-ligand interactions with the activation of adenylyl cyclase and a variety of cellular reponses. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene result in pseudohypoparathyroidism type 1a, pseudohypoparathyroidism type 1b, Albright hereditary osteodystrophy, pseudopseudohypoparathyroidism, McCune-Albright syndrome, progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone, and some pituitary tumors. [provided by RefSeq, Aug 2012]

HNF1A

The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5′-GTTAATNATTAAC-3′. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

HRAS

This gene belongs to the Ras oncogene family, whose members are related to the transforming genes of mammalian sarcoma retroviruses. The products encoded by these genes function in signal transduction pathways. These proteins can bind GTP and GDP, and they have intrinsic GTPase activity. This protein undergoes a continuous cycle of de- and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus. Mutations in this gene cause Costello syndrome, a disease characterized by increased growth at the prenatal stage, growth deficiency at the postnatal stage, predisposition to tumor formation, mental retardation, skin and musculoskeletal abnormalities, distinctive facial appearance and cardiovascular abnormalities. Defects in this gene are implicated in a variety of cancers, including bladder cancer, follicular thyroid cancer, and oral squamous cell carcinoma. Multiple transcript variants, which encode different isoforms, have been identified for this gene. [provided by RefSeq, Jul 2008]

IDH1

Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. Each NADP(+)-dependent isozyme is a homodimer. The protein encoded by this gene is the NADP(+)-dependent isocitrate dehydrogenase found in the cytoplasm and peroxisomes. It contains the PTS-1 peroxisomal targeting signal sequence. The presence of this enzyme in peroxisomes suggests roles in the regeneration of NADPH for intraperoxisomal reductions, such as the conversion of 2, 4-dienoyl-CoAs to 3-enoyl-CoAs, as well as in peroxisomal reactions that consume 2-oxoglutarate, namely the alpha-hydroxylation of phytanic acid. The cytoplasmic enzyme serves a significant role in cytoplasmic NADPH production. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]

IDH2

Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. Each NADP(+)-dependent isozyme is a homodimer. The protein encoded by this gene is the NADP(+)-dependent isocitrate dehydrogenase found in the mitochondria. It plays a role in intermediary metabolism and energy production. This protein may tightly associate or interact with the pyruvate dehydrogenase complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

JAK2

This gene product is a protein tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. It has been found to be constituitively associated with the prolactin receptor and is required for responses to gamma interferon. Mice that do not express an active protein for this gene exhibit embryonic lethality associated with the absence of definitive erythropoiesis. [provided by RefSeq, Jul 2008]

JAK3

The protein encoded by this gene is a member of the Janus kinase (JAK) family of tyrosine kinases involved in cytokine receptor-mediated intracellular signal transduction. It is predominantly expressed in immune cells and transduces a signal in response to its activation via tyrosine phosphorylation by interleukin receptors. Mutations in this gene are associated with autosomal SCID (severe combined immunodeficiency disease). [provided by RefSeq, Jul 2008]

KDR

Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell protein tyrosine phosphatase, etc.. Mutations of this gene are implicated in infantile capillary hemangiomas. [provided by RefSeq, May 2009]

KIT

This gene encodes the human homolog of the proto-oncogene c-kit. C-kit was first identified as the cellular homolog of the feline sarcoma viral oncogene v-kit. This protein is a type 3 transmembrane receptor for MGF (mast cell growth factor, also known as stem cell factor). Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous lukemia, and piebaldism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KRAS

This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]

MET

This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that are linked via disulfide bonds to form the mature receptor. Further processing of the beta subunit results in the formation of the M10 peptide, which has been shown to reduce lung fibrosis. Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. Mutations in this gene are associated with papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers. Amplification and overexpression of this gene are also associated with multiple human cancers. [provided by RefSeq, May 2016]

MLH1

The protein encoded by this gene can heterodimerize with mismatch repair endonuclease PMS2 to form MutL alpha, part of the DNA mismatch repair system. When MutL alpha is bound by MutS beta and some accessory proteins, the PMS2 subunit of MutL alpha introduces a single-strand break near DNA mismatches, providing an entry point for exonuclease degradation. The encoded protein is also involved in DNA damage signaling and can heterodimerize with DNA mismatch repair protein MLH3 to form MutL gamma, which is involved in meiosis. This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). [provided by RefSeq, Aug 2017]

MPL

In 1990 an oncogene, v-mpl, was identified from the murine myeloproliferative leukemia virus that was capable of immortalizing bone marrow hematopoietic cells from different lineages. In 1992 the human homologue, named, c-mpl, was cloned. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptor superfamily. Presence of anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte colony formation. The ligand for c-mpl, thrombopoietin, was cloned in 1994. Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation. The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs . TPO-R deficient mice were severely thrombocytopenic, emphasizing the important role of CD110 and thrombopoietin in megakaryocyte and platelet formation. Upon binding of thrombopoietin CD110 is dimerized and the JAK family of non-receptor tyrosine kinases, as well as the STAT family, the MAPK family, the adaptor protein Shc and the receptors themselves become tyrosine phosphorylated. [provided by RefSeq, Jul 2008]

NOTCH1

This gene encodes a member of the NOTCH family of proteins. Members of this Type I transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple different domain types. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor plays a role in the development of numerous cell and tissue types. Mutations in this gene are associated with aortic valve disease, Adams-Oliver syndrome, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and head and neck squamous cell carcinoma. [provided by RefSeq, Jan 2016]

NPM1

The protein encoded by this gene is involved in several cellular processes, including centrosome duplication, protein chaperoning, and cell proliferation. The encoded phosphoprotein shuttles between the nucleolus, nucleus, and cytoplasm, chaperoning ribosomal proteins and core histones from the nucleus to the cytoplasm. This protein is also known to sequester the tumor suppressor ARF in the nucleolus, protecting it from degradation until it is needed. Mutations in this gene are associated with acute myeloid leukemia. Dozens of pseudogenes of this gene have been identified. [provided by RefSeq, Aug 2017]

NRAS

This is an N-ras oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. This shuttling is regulated through palmitoylation and depalmitoylation by the ZDHHC9-GOLGA7 complex. The encoded protein, which has intrinsic GTPase activity, is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase activating protein. Mutations in this gene have been associated with somatic rectal cancer, follicular thyroid cancer, autoimmune lymphoproliferative syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia. [provided by RefSeq, Jun 2011]

PDGFRA

This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers. [provided by RefSeq, Mar 2012]

PIK3CA

Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]

PTEN

This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]

PTPN11

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migration. Mutations in this gene are a cause of Noonan syndrome as well as acute myeloid leukemia. [provided by RefSeq, Aug 2016]

RB1

The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. [provided by RefSeq, Jul 2008]

RET

This gene encodes a transmembrane receptor and member of the tyrosine protein kinase family of proteins. Binding of ligands such as GDNF (glial cell-line derived neurotrophic factor) and other related proteins to the encoded receptor stimulates receptor dimerization and activation of downstream signaling pathways that play a role in cell differentiation, growth, migration and survival. The encoded receptor is important in development of the nervous system, and the development of organs and tissues derived from the neural crest. This proto-oncogene can undergo oncogenic activation through both cytogenetic rearrangement and activating point mutations. Mutations in this gene are associated with Hirschsprung disease and central hypoventilation syndrome and have been identified in patients with renal agenesis. [provided by RefSeq, Sep 2017]

SMAD4

This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor (TGF)-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The protein acts as a tumor suppressor and inhibits epithelial cell proliferation. It may also have an inhibitory effect on tumors by reducing angiogenesis and increasng blood vessel hyperpermeability. The encoded protein is a crucial component of the bone morphogenetic protein signaling pathway. The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq, Aug 2017]

SMARCB1

The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

SMO

The protein encoded by this gene is a G protein-coupled receptor that interacts with the patched protein, a receptor for hedgehog proteins. The encoded protein tranduces signals to other proteins after activation by a hedgehog protein/patched protein complex. [provided by RefSeq, Jul 2010]

SRC

This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

STK11

This gene, which encodes a member of the serine/threonine kinase family, regulates cell polarity and functions as a tumor suppressor. Mutations in this gene have been associated with Peutz-Jeghers syndrome, an autosomal dominant disorder characterized by the growth of polyps in the gastrointestinal tract, pigmented macules on the skin and mouth, and other neoplasms. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

TP53

This gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. Mutations in this gene are associated with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation initiation codons from identical transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016]

VHL

Von Hippel-Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign tumors. A germline mutation of this gene is the basis of familial inheritance of VHL syndrome. The protein encoded by this gene is a component of the protein complex that includes elongin B, elongin C, and cullin-2, and possesses ubiquitin ligase E3 activity. This protein is involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the regulation of gene expression by oxygen. RNA polymerase II subunit POLR2G/RPB7 is also reported to be a target of this protein. Alternatively spliced transcript variants encoding distinct isoforms have been observed.
[provided by RefSeq, Jul 2008]

RESOURCES AND MATERIALS