Invitae Common Hereditary Cancers Panel (Breast, Gyn, GI)


Test description

The Invitae Common Hereditary Cancers Panel analyzes 42 genes that are associated with cancers of the breast, ovary, uterus, and gastrointestinal system, which includes the stomach, colon, rectum, small bowel, and pancreas. The panel is designed to maximize diagnostic yield for patients 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.

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Primary panel (42 genes)


APC: Deletion/duplication analysis covers the 1A and 1B promoter regions.
BMPR1A: Deletion/duplication analysis covers the promoter region.
CDKN2A: Analysis supports interpretation of the p16 protein only
EPCAM: Analysis is limited to deletion/duplication analysis
GREM1: Analysis of this gene is limited to deletion/duplication analysis of the promoter region.
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
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.

  • Ataxia-telangiectasia (A-T)
  • Cowden and Cowden-like syndrome
  • DICER1 syndrome
  • Familial adenomatous polyposis (FAP)
  • Familial gastrointestinal stromal tumors (GIST)
  • Hereditary breast and ovarian cancer syndrome (HBOC)
  • Hereditary diffuse gastric cancer (HGDC)
  • Juvenile polyposis syndrome (JPS)
  • Li-Fraumeni syndrome (LFS)
  • Lynch syndrome
  • 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 42 genes that are associated with hereditary breast, ovarian, uterine, colorectal, gastric, and pancreatic cancers. Although most breast, gynecologic, and gastrointestinal cancers are sporadic and not inherited, 5%-10% are due to an identifiable pathogenic variant. Individuals with a pathogenic variant in one of the genes on this panel have an increased risk of developing cancer, 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%. Most cases are sporadic and not inherited; however, approximately 5%-10% of breast cancer is hereditary and due to an identifiable pathogenic variant. 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 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.

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 in which pathogenic variants increase 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.

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 present differently, even among individuals within the same family. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may benefit most patients who are found to have a pathogenic variant.

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

All of the genes on this panel have autosomal dominant inheritance for hereditary breast, ovarian, ovarian, uterine, and gastrointestinal cancers. Several of these genes also 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).
  • EPCAM is associated with congenital tufting enteropathy (CTE).
  • MUTYH is associated with MUTYH-associated polyposis (MAP).
  • 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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

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
CDKN2A* NM_000077.4, NM_058195.3
CHEK2 NM_007194.3
DICER1 NM_177438.2
EPCAM* NM_002354.2
GREM1* NM_013372.6
KIT NM_000222.2
MEN1 NM_130799.2
MLH1* NM_000249.3
MSH2* NM_000251.2
MSH6 NM_000179.2
MUTYH NM_001128425.1
NBN NM_002485.4
NF1 NM_000267.3
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: Deletion/duplication analysis covers the 1A and 1B promoter regions.
BMPR1A: Deletion/duplication analysis covers the promoter region.
CDKN2A: Analysis supports interpretation of the p16 protein only
EPCAM: Analysis is limited to deletion/duplication analysis
GREM1: Analysis of this gene is limited to deletion/duplication analysis of the promoter region.
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
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.