• Mitigating Risk for Cancer Patients

Hereditary Cancer

The mapping of the human genome has provided medical professionals with the ability to refine a patient’s cancer risk through the analysis of inherited mutations.

Luminus’ genetic tests screen a number of known genes related to hereditary cancers. The goal of every test is to determine a patient’s risk of cancer. This knowledge can help your physician to develop the appropriate or preventative treatment plan for early detection. If the results of your test indicate an increased risk for cancer, your doctor may order tests like mammograms, colonoscopy and CT scans for any possible diagnosis and immediate intervention.

Our Tests

Hereditary Breast Cancer (BRCA 1/2)

(Ashkenazi Jewish, Hispanic with Reflexive options)

Hereditary Breast + Ovarian/Endometrial Cancer

Hereditary Pan Cancer

Hereditary Prostate Cancer

Hereditary Pancreatic Cancer

Hereditary Colorectal / Lynch Syndrome Cancer Panel

Hereditary Breast Cancer (BRCA1/2)

(Ashkenazi Jewish, Hispanic with Reflexive options)

Having mutations in either the BRCA1 or the BRCA2 gene significantly increases a patient’s risk for breast, ovarian and other types of cancer.

WHAT IS TESTED?

BRCA1 description

Pathogenic variants in the BRCA1 gene are associated with hereditary breast and ovarian cancer (HBOC) syndrome, and convey a significantly increased risk of both breast and ovarian cancer. Studies have demonstrated that BRCA1 gene pathogenic variants can be associated with up to an 85% breast cancer risks and up to a 63% ovarian cancer risks. Furthermore, women with a BRCA1 pathogenic variant have an increased risk of a second breast cancer diagnosis (contralateral or ipsilateral). This risk has estimated to be up to 27% within the first 5 years of diagnosis and up to 40-50% within 20 years of initial diagnosis. Pathogenic variants in BRCA1 may also be associated with an increased risk of other types of cancer, including peritoneal, pancreatic, prostate, and male breast cancer. However, the exact level of risk is not yet known.

BRCA2 description

Pathogenic variants in the BRCA2 gene are associated with Hereditary Breast and Ovarian Cancer (HBOC) syndrome, and convey a significantly increased risk of several cancers, including breast, ovarian, pancreatic, melanoma, and prostate cancer. Studies have demonstrated that BRCA2 gene pathogenic variants can be associated with up to an 84% breast cancer risk and up to a 27% ovarian cancer risk. Furthermore, in women who have had breast cancer, having a BRCA2 pathogenic variant increases risk of a second breast cancer diagnosis (contralateral or ipsilateral). This risk has estimated to be up to 12% within the first 5 years of diagnosis and up to 40–50% within 20 years of initial diagnosis. BRCA2 pathogenic variants may also be associated with small increased risks of developing primary peritoneal, gallbladder, bile duct, and stomach cancer. However, these risks are not yet clearly defined. 

Inheritance and Familial Implications

BRCA1 and BRCA2 pathogenic variants are inherited in a dominant pattern, meaning that anyone with a pathogenic variant has a 50% chance of passing it on to each of his or her children. Conversely, this also means that they have a 50% chance of not passing on the pathogenic variant to each child. Individuals who carry a BRCA1 or BRCA2 pathogenic variant do not have any control over whether or not a variant is passed on to their children. Both men and women can have pathogenic variants in BRCA1 or BRCA2 and can pass them down to their children, even though the cancer risks may be different for males and females. In addition to children, each first-degree relative (parents and full siblings) of someone with a BRCA1 or BRCA2 pathogenic variant has a 50% chance to have the same pathogenic variant.

Genetic testing is available to at-risk family members to determine if they also carry the identified BRCA1 or BRCA2 pathogenic variant. Because of the increased risks for certain cancers, identified carriers of the BRCA1 or BRCA2 should seek recommendations from their provider regarding future medical management. Those individuals found not to carry the familial BRCA1 or BRCA2 gene pathogenic variant will have risks similar to the general population.

WHO IS IT FOR?

BRCA High Risk Patient Criteria

The test is best suited for individuals with either a history of early onset breast or ovarian cancer or a strong family history of breast and/or ovarian cancer. Individuals with the following medical or family history factors should consider testing for mutations in BRCA1/2:

  • Early onset breast cancer (under 50 years of age)
  • Bilateral or multiple breast cancers
  • Diagnosed with both breast and ovarian cancer
  • Family history of breast and/or ovarian cancer
  • Two or more BRCA1 or BRCA2 related cancers in a single family member
  • Male breast cancer within family
  • Ashkenazi Jewish ethnic background

Clinical Utility of BRCA Testing

  • Guide decisions on prevention strategies (e.g. chemoprevention, prophylactic surgery)
  • Increase surveillance for breast cancer
  • Inform treatment decisions
  • Identify family members at increased risk

Familial Studies Program

In the process of sequencing the patient’s DNA, we may identify a likely pathogenic genetic variant, or a genetic variant with uncertain pathogenicity (VUS). To help understand the significance of these types of variants, and how the patient and family members may be affected, Luminus offers a Familial Studies Program. Testing additional family members for the same variant observed in your patient, and determining the correlation between cancer history and occurrence of the variant, may provide further insight into the clinical relevance of the variant.

VARIANT CLASSIFICATIONS

Classification System

Luminus Diagnostics classifies variants using a 5-tier system based on the American College of Medical Genetics (ACMG) guidelines. Likely Benign and Benign variants are not reported.

Pathogenic
Mutations with known clinical significance and demonstrated to increase the risk of cancer

Likely Pathogenic
Genetic changes that have some preliminary clinical data suggesting an association with cancer but not sufficient to make a definitive determination of pathogenicity and associated cancer risk

Uncertain Pathogenicity (VUS) | Genetic changes with either conflicting data or no supporting data, thus a determination of pathogenicity cannot be made

Likely Benign
Genetic changes with strong but limited evidence to be classified as benign and are not likely to increase the risk for cancer

Benign
Genetic changes that are previously reported and have sufficient evidence to be classified as benign with no clinical relevance

Hereditary Breast + Ovarian/Endometrial Cancer

WHAT IS TESTED?

Hereditary Breast Ovarian Endometrial cancer tests analyze the coding and flanking regions (+/- 20 bp) of 19 genes associated with hereditary colorectal cancer (ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PALB2, POLD1, PTEN, RAD51C, RAD51D, STK11, TP53) by next-generation sequencing-based (NGS) and Sanger confirmation of reported gene variants. Sanger fill-in is used for all genes in areas of low coverage, which is defined as a read depth of less than 25x. Gross deletions and duplications in the aforementioned 19 genes and EPCAM are identified by microarray analysis and multiplex ligation-dependent probe amplification (MLPA). Suspected deletions in exons 13-15 of PMS2 are confirmed with long range PCR to exclude the pseudogene signal.

WHO IS THIS FOR?

The test is best suited for individuals with either a history of early onset breast, ovarian or endometrial cancer or a strong family history of breast, ovarian, and /or endometrial cancer. Individuals with the
following medical or family history factors should consider testing for mutations in BRCA1/2:

  • Early onset breast, ovarian, or endometrial cancer (under 50 years of age)
  • Bilateral or multiple breast, ovarian cancers
  • Diagnosed with breast, ovarian, and/or endometrial cancer
  • Family history of breast, ovarian or endometrial cancer
  • Two or more BRCA1 or BRCA2 related cancers in a single family member

Clinical Utility of Hereditary Breast Ovarian Endometrial Testing

  • Guide decisions on prevention strategies (e.g. chemoprevention, prophylactic surgery)
  • Increase surveillance for breast, ovarian, endometrial cancer
  • Inform treatment decisions
  • Identify family members at increased risk

VARIANT CLASSIFICATIONS

Classification System

Luminus Diagnostics classifies variants using a 5-tier system based on the American College of Medical Genetics (ACMG) guidelines. Likely Benign and Benign variants are not reported.

Pathogenic
Mutations with known clinical significance and demonstrated to increase the risk of cancer

Likely Pathogenic
Genetic changes that have some preliminary clinical data suggesting an association with cancer but not sufficient to make a definitive determination of pathogenicity and associated cancer risk

Uncertain Pathogenicity (VUS)
Genetic changes with either conflicting data or no supporting data, thus a determination of pathogenicity cannot be made

Likely Benign
Genetic changes with strong but limited evidence to be classified as benign and are not likely to increase the risk for cancer

Benign
Genetic changes that are previously reported and have sufficient evidence to be classified as benign with no clinical relevance

Hereditary Pan Cancer

WHAT IS TESTED?

Hereditary Pan cancer tests analyze the coding and flanking regions (+/- 20 bp) of 26 genes associated with hereditary colorectal cancer (APC, ATM, BMPR1A, BRAC1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, POLD1, POLE, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53, VHL) by next-generation sequencing-based (NGS) and Sanger confirmation of reported gene variants. Sanger fill-in is used for all genes in areas of low coverage, which is defined as a read depth of less than 25x. Gross deletions and duplications in the aforementioned 26 genes and EPCAM are identified by microarray analysis and multiplex ligation-dependent probe amplification (MLPA). Suspected deletions in exons 13-15 of PMS2 are confirmed with long range PCR to exclude the pseudogene signal.

WHO IS THIS FOR?

Individuals who meet one or more of the following criteria should consider genetic testing for colorectal cancer:

History of early onset breast, colorectal, endometrial, ovarian, pancreatic, prostate or other related cancers and / or Lynch syndrome

  • History of two or more associated cancers
  • Two or more relatives with associated cancers, with one diagnosed <50yrs
  • Multiple family members, on the same side of the family, with the same type of cancer or
    associated cancers

Clinical Utility of Pan Cancer Testing

  • Guide decisions on prevention strategies (e.g. chemoprevention, prophylactic surgery)
  • Increase surveillance for hereditary cancers
  • Inform treatment decisions
  • Identify family members at increased risk

VARIANT CLASSIFICATIONS

Classification System

Luminus Diagnostics classifies variants using a 5-tier system based on the American College of Medical Genetics (ACMG) guidelines. Likely Benign and Benign variants are not reported.

Pathogenic
Mutations with known clinical significance and demonstrated to increase the risk of cancer

Likely Pathogenic
Genetic changes that have some preliminary clinical data suggesting an association with cancer but not sufficient to make a definitive determination of pathogenicity and associated cancer risk

Uncertain Pathogenicity (VUS)
Genetic changes with either conflicting data or no supporting data,
thus a determination of pathogenicity cannot be made

Likely Benign
Genetic changes with strong but limited evidence to be classified as benign and are not likely to increase the risk for cancer

Benign
Genetic changes that are previously reported and have sufficient evidence to be classified as benign with no clinical relevance

Hereditary Pancreatic Cancer

WHAT IS TESTED?

Hereditary Pancreatic cancer tests analyze the coding and flanking regions (+/- 20 bp) of 15 genes associated with hereditary colorectal cancer (APC, ATM, BRCA1, BRCA2, CDK4, CDKN2NA, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, TP53, VHL) by next-generation sequencing-based (NGS) and

Sanger confirmation of reported gene variants. Sanger fill-in is used for all genes in areas of low coverage, which is defined as a read depth of less than 25x. Gross deletions and duplications in the aforementioned 15 genes and EPCAM are identified by microarray analysis and multiplex ligation-dependent probe amplification (MLPA). Suspected deletions in exons 13-15 of PMS2 are confirmed with long range PCR to exclude the pseudogene signal.

WHO IS THIS FOR?

The test is best suited for individuals with either a history of pancreatic cancer or a strong family history
of pancreatic cancer. Individuals with the following medical or family history factors should consider
testing for mutations in BRCA1/2:

  • Pancreatic cancer
  • Family history of pancreatic cancer (under 50 years of age)

Clinical Utility of Pancreatic Testing

  • Guide decisions on prevention strategies (e.g. chemoprevention, prophylactic surgery)
  • Increase surveillance for pancreatic cancer
  • Inform treatment decisions
  • Identify family members at increased risk

VARIANT CLASSIFICATIONS

Classification System

Luminus Diagnostics classifies variants using a 5-tier system based on the American College of Medical Genetics (ACMG) guidelines. Likely Benign and Benign variants are not reported.

Pathogenic
Mutations with known clinical significance and demonstrated to increase the risk of cancer

Likely Pathogenic
Genetic changes that have some preliminary clinical data suggesting an association with cancer but not
sufficient to make a definitive determination of pathogenicity and associated cancer risk

Uncertain Pathogenicity (VUS)
Genetic changes with either conflicting data or no supporting data, thus a determination of pathogenicity cannot be made

Likely Benign
Genetic changes with strong but limited evidence to be classified as benign and are not likely to increase the risk for cancer

Benign
Genetic changes that are previously reported and have sufficient evidence to be classified as benign with no clinical relevance

Hereditary Prostate Cancer

WHAT IS TESTED?

Hereditary prostate cancer tests analyze the coding and flanking regions (+/- 20 bp) of 14 genes associated with hereditary colorectal cancer (ATM, BRCA1, BRCA2, BRIP1, CHEK2, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, RAD51C, RAD51D, TP53) by next-generation sequencing-based (NGS) and Sanger confirmation of reported gene variants. Sanger fill-in is used for all genes in areas of low coverage, which is defined as a read depth of less than 25x. Gross deletions and duplications in the aforementioned 14 genes and EPCAM are identified by microarray analysis and multiplex ligation-dependent probe amplification (MLPA). Suspected deletions in exons 13-15 of PMS2 are confirmed with long range PCR to exclude the pseudogene signal.

WHO IS THIS FOR?

The test is best suited for individuals with either a history of prostate cancer or a strong family history of prostate cancer. Individuals with the following medical or family history factors should consider testing for mutations:

  • Prostate cancer
  • Family history of Prostate cancer (under age 50)

Clinical Utility of Pancreatic Testing

  • Guide decisions on prevention strategies (e.g. chemoprevention, prophylactic surgery)
  • Increase surveillance for pancreatic cancer
  • Inform treatment decisions
  • Identify family members at increased risk

VARIANT CLASSIFICATIONS?

Classification System

Luminus Diagnostics classifies variants using a 5-tier system based on the American College of Medical Genetics (ACMG) guidelines. Likely Benign and Benign variants are not reported.

Pathogenic
Mutations with known clinical significance and demonstrated to increase the risk of cancer

Likely Pathogenic
Genetic changes that have some preliminary clinical data suggesting an association with cancer but not sufficient to make a definitive determination of pathogenicity and associated cancer risk

Uncertain Pathogenicity (VUS)
Genetic changes with either conflicting data or no supporting data, thus a determination of pathogenicity cannot be made

Likely Benign
Genetic changes with strong but limited evidence to be classified as benign and are not likely to increase the risk for cancer

Benign
Genetic changes that are previously reported and have sufficient evidence to be classified as benign with no clinical relevance

Hereditary Colorectal / Lynch Syndrome

WHAT IS TESTED?

According to the Centers for Disease Control and Prevention (CDC) and the American Cancer Society, colorectal cancer is the second leading cause of cancer-related death in the United States, and the third most commonly diagnosed cancer in men and women. Overall, 1 in 20 individuals will develop colorectal cancer at some point during their life – equating to a 5% lifetime risk of developing colorectal cancer.

Although the majority of colorectal cancer is sporadic, and caused by a variety of genetic and non-genetic factors, research has shown that approximately 5% of colorectal cancers are due to hereditary changes in single genes.

Hereditary Colorectal / Lynch Syndrome tests analyze the coding and flanking regions (+/- 20 bp) of 17 genes associated with hereditary colorectal cancer (APC, ATM, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, POLD1, POLE, PTEN, SMAD4, STK11, TP53) by next-generation sequencing- based (NGS) and Sanger confirmation of reported gene variants. Sanger fill-in is used for all genes in areas of low coverage, which is defined as a read depth of less than 25x. Gross deletions and duplications in the aforementioned 17 genes and EPCAM are identified by microarray analysis and multiplex ligation-dependent probe amplification (MLPA). Suspected deletions in exons 13-15 of PMS2 are confirmed with long range PCR to exclude the pseudogene signal.

WHO IS THIS FOR?

Individuals who meet one or more of the following criteria should consider genetic testing for colorectal cancer:

  • History of early onset colorectal or endometrial cancer
  • History of ≥ 10 adenomas or polyps
  • History of two or more associated cancers
  • Two or more relatives with associated cancers, with one diagnosed <50yrs
  • History of colon adenomas under 50 year of age
  • Multiple family members, on the same side of the family, with the same type of cancer or associated cancers
  • Abnormal MSI and/or IHC testing

Clinical Utility of Colorectal / Lynch Syndrome Testing

Guide decisions on prevention strategies (e.g. chemoprevention, prophylactic surgery)

Increase surveillance for colorectal cancer

Inform treatment decisions

Identify family members at increased risk

VARIANT CLASSIFICATIONS

Classification System

Luminus Diagnostics classifies variants using a 5-tier system based on the American College of Medical Genetics (ACMG) guidelines. Likely Benign and Benign variants are not reported.

Pathogenic
Mutations with known clinical significance and demonstrated to increase the risk of cancer

Likely Pathogenic
Genetic changes that have some preliminary clinical data suggesting an association with cancer but not
sufficient to make a definitive determination of pathogenicity and associated cancer risk

Uncertain Pathogenicity (VUS)
Genetic changes with either conflicting data or no supporting data, thus a determination of pathogenicity cannot be made

Likely Benign
Genetic changes with strong but limited evidence to be classified as benign and are not likely to increase the risk for cancer

Benign
Genetic changes that are previously reported and have sufficient evidence to be classified as benign with no clinical relevance