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  1. Test Catalog
  2. Invitae Common Hereditary Cancers Panel

Invitae Common Hereditary Cancers Panel

Test description

The Invitae Common Hereditary Cancers Panel analyzes 47 genes associated with cancers of the breast, ovary, uterus, prostate, and gastrointestinal system, which includes the stomach, colon, rectum, small bowel, and pancreas. The panel is designed to maximize diagnostic yield for individuals with a personal or family history of mixed cancers affecting these organ systems.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

Genes tested

APC ATM AXIN2 BARD1 BMPR1A BRCA1 BRCA2 BRIP1 CDH1 CDK4 CDKN2A CHEK2 CTNNA1 DICER1 EPCAM GREM1 HOXB13 KIT MEN1 MLH1 MSH2 MSH3 MSH6 MUTYH NBN NF1 NTHL1 PALB2 PDGFRA PMS2 POLD1 POLE PTEN RAD50 RAD51C RAD51D SDHA SDHB SDHC SDHD SMAD4 SMARCA4 STK11 TP53 TSC1 TSC2 VHL

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Primary panel (47 genes)

APC ATM AXIN2 BARD1 BMPR1A BRCA1 BRCA2 BRIP1 CDH1 CDK4 CDKN2A CHEK2 CTNNA1 DICER1 EPCAM GREM1 HOXB13 KIT MEN1 MLH1 MSH2 MSH3 MSH6 MUTYH NBN NF1 NTHL1 PALB2 PDGFRA PMS2 POLD1 POLE PTEN RAD50 RAD51C RAD51D SDHA SDHB SDHC SDHD SMAD4 SMARCA4 STK11 TP53 TSC1 TSC2 VHL

Panel details and technical assay limitations

Clinical information

  • ataxia-telangiectasia (A-T)
  • constitutional mismatch repair deficiency (CMMR-D)
  • Cowden and Cowden-like syndrome
  • DICER1 syndrome
  • familial adenomatous polyposis (FAP)
  • familial gastrointestinal stromal tumors (GIST)
  • Fanconi anemia
  • hereditary breast and ovarian cancer syndrome (HBOC)
  • hereditary diffuse gastric cancer (HGDC)
  • juvenile polyposis syndrome (JPS)
  • Li-Fraumeni syndrome (LFS)
  • Lynch syndrome – also known as hereditary non-polyposis colorectal cancer (HNPCC)
  • melanoma-pancreatic cancer syndrome (M-PCS)
  • multiple endocrine neoplasia type 1 (MEN1)
  • MUTYH-associated polyposis (MAP)
  • neurofibromatosis type 1 (NF1)
  • Nijmegen breakage syndrome (NBS)
  • oligodontia-colorectal cancer syndrome
  • Peutz-Jeghers syndrome (PJS)
  • rhabdoid tumor predisposition syndrome (RTPS)
  • tuberous sclerosis complex (TSC)
  • von Hippel-Lindau syndrome (VHL)

The Invitae Common Hereditary Cancers panel analyzes 47 genes associated with hereditary breast, ovarian, uterine, prostate, colorectal, gastric, melanoma, and pancreatic cancers. Individuals with a pathogenic variant in one of these genes have an increased risk of developing certain cancers, many of which may be difficult both to detect and to treat. Identifying those at high risk enables implementation of additional screening, surveillance, and interventions. These efforts may result in risk-reduction and early diagnosis, increasing the chances of successful treatment and survival.

Breast cancer: The average woman’s lifetime risk of developing breast cancer is 12%. Although there are a number of other genes associated with hereditary breast cancer, hereditary breast and ovarian cancer syndrome (HBOC) due to pathogenic variants in BRCA1 and BRCA2 accounts for most cases in individuals with a strong family history or an early-onset diagnosis.

Ovarian: The general population risk for ovarian cancer is 1.3%. Lynch syndrome and hereditary breast and ovarian cancer syndrome (HBOC) due to pathogenic variants in the BRCA1 and BRCA2 genes are common causes of inherited ovarian cancer, as are several other hereditary cancer genes.

Uterine: The general population risk for uterine cancer is 2.7%. Lynch syndrome is the most common inherited cause of uterine cancer, although there are a number of other hereditary cancer genes associated with this cancer type.

Prostate: A man’s lifetime risk for developing prostate cancer is 1 in 7 (15%). Inherited pathogenic variants in certain genes — particularly ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PMS2, and TP53 — account for some cases of hereditary prostate cancer. Men with pathogenic variants in these genes have an increased risk of developing prostate cancer and, in some cases, other cancers as well.

Colorectal: Colorectal cancer (CRC) is the third-most-common cancer diagnosis in the United States. Hereditary colorectal cancer syndromes are generally divided into two types, Lynch syndrome and polyposis syndromes. Lynch syndrome, also called hereditary non-polyposis colon cancer (HNPCC), is caused by pathogenic variants in MLH1, MSH2, MSH6, PMS2, and EPCAM and is the most common inherited cause of colorectal cancer. Polyposis syndromes are characterized by the development of numerous precancerous polyps, which may become malignant.

Gastric: Gastric cancer occurs in approximately 1 in 93 individuals in the general population. Gastric adenocarcinomas account for 90%-95% of gastric cancers and are further histologically divided into intestinal type and diffuse type. The most common cause of hereditary gastric cancer is a pathogenic variant in CDH1, which causes hereditary diffuse gastric cancer syndrome, but there are a number of other genes associated with an increased risk for gastric tumors. Gastrointestinal stromal tumors (GISTs) are characterized as sarcomas and are rare tumors of the GI tract that account for 1%-3% of all gastric cancers. The Invitae Common Hereditary Cancers panel includes genes that increase risk for each of these types of gastric tumors.

Pancreatic: There are two main types of pancreatic cancer: cancer of the exonic pancreas (pancreatic adenocarcinoma), which accounts for 95% of pancreatic tumors, and pancreatic neuroendocrine tumors. Hereditary pancreatic cancer can be caused by BRCA2 and CDKN2A, as well as by several other genes. The Invitae Common Hereditary Cancers panel analyzes the genes that are most commonly associated with an increased risk for both types of pancreatic cancer.

Melanoma: Most cases of melanoma are isolated and sporadic. The number of individuals who have an inherited risk of melanoma is unknown, but it is thought to be low. Most heritable cases are due to pathogenic variants in the CKDN2A gene as well as several other genes.

Individuals with a pathogenic variant identified by the Invitae Common Hereditary Cancers Panel have an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develop cancer. Further, the same variant may manifest with different symptoms, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may be beneficial.

For gene-associated cancer risks, download our Cancer risk poster.

All of the genes on this panel have autosomal dominant inheritance for hereditary cancer predisposition. Several of these genes also have autosomal recessive inheritance, or result in clinically distinct autosomal recessive conditions:

  • BRCA2, BRIP1, FANCC, PALB2, and RAD51C are associated with Fanconi anemia.
  • ATM and MRE11A are associated with ataxia-telangiectasia and ataxia-telangiectasia-like disorder (ATLD), respectively.
  • MLH1, MSH2, PMS2, and MSH6 are associated with constitutional mismatch repair deficiency (CMMR-D).
  • MUTYH is associated with MUTYH-associated polyposis (MAP).
  • MSH3 is associated with MSH3-associated polyposis.
  • NTHL1 is associated with NTHL1-associated polyposis.
  • NBN and RAD50 are associated with Nijmegen breakage syndrome and Nijmegen breakage syndrome-like disorder (NBSLD), respectively.

This panel may be considered for individuals with:

  • a clinical history indicative of a hereditary cancer syndrome but a limited pedigree due to small family size or adoption
  • a family history presenting with multiple cancer types that could fit the features of more than one hereditary cancer syndrome

There are also some common general features suggestive of a family with hereditary cancer syndrome. These include:

  • cancer diagnosed at an unusually young age
  • different types of cancer that have occurred independently in the same person
  • cancer that has developed in both organs of a set of paired organs (e.g., both kidneys, both breasts)
  • several close blood relatives that have the same type of cancer
  • unusual cases of a specific cancer type (e.g., male breast cancer)

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Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
APC* NM_000038.5
ATM NM_000051.3
AXIN2 NM_004655.3
BARD1 NM_000465.3
BMPR1A* NM_004329.2
BRCA1* NM_007294.3
BRCA2* NM_000059.3
BRIP1 NM_032043.2
CDH1 NM_004360.3
CDK4 NM_000075.3
CDKN2A* NM_000077.4; NM_058195.3
CHEK2 NM_007194.3
CTNNA1 NM_001903.3
DICER1 NM_177438.2
EPCAM* NM_002354.2
GREM1* NM_013372.6
HOXB13* NM_006361.5
KIT NM_000222.2
MEN1 NM_130799.2
MLH1* NM_000249.3
MSH2* NM_000251.2
MSH3 NM_002439.4
MSH6 NM_000179.2
MUTYH NM_001128425.1
NBN NM_002485.4
NF1 NM_000267.3
NTHL1* NM_002528.6
PALB2 NM_024675.3
PDGFRA NM_006206.4
PMS2 NM_000535.5
POLD1 NM_002691.3
POLE NM_006231.3
PTEN* NM_000314.4
RAD50 NM_005732.3
RAD51C NM_058216.2
RAD51D NM_002878.3
SDHA* NM_004168.3
SDHB NM_003000.2
SDHC NM_003001.3
SDHD NM_003002.3
SMAD4 NM_005359.5
SMARCA4 NM_001128849.1
STK11 NM_000455.4
TP53* NM_000546.5
TSC1 NM_000368.4
TSC2 NM_000548.3
VHL NM_000551.3

APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis.
BMPR1A: Deletion/duplication analysis covers the promoter region.
BRCA1: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
BRCA2: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
CDKN2A: Analysis supports interpretation of the p14 and p16 proteins.
EPCAM: Analysis is limited to deletion/duplication analysis.
GREM1: Analysis of this gene is limited to deletion/duplication analysis of the promoter region.
HOXB13: Analysis is limited to the NM_006361.5:c.251G>A, p.Gly84Glu variant.
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
NTHL1: Deletion/duplication analysis is not offered for this gene.
PTEN: Deletion/duplication analysis covers the promoter region.
SDHA: Analysis is limited to sequencing analysis. No clinically-relevant del/dups have been reported.
TP53: Deletion/duplication analysis covers the promoter region.

Clinical resources
Genes and associated cancers chart Hereditary cancer gene list Hereditary cancer risks and references chart Invitae brochure
Patient resources
Patient guide: Genetic testing for hereditary cancer Patient guide: Genetic testing simplified Patient guide: Hereditary breast cancer Patient guide: Hereditary colorectal cancer
Test information
Forms page Specimen requirements page

References

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