The Invitae Gastric Cancer Panel analyzes genes associated with an increased lifetime risk of developing stomach cancer. These genes were selected based on the available evidence to date to provide Invitae’s broadest hereditary gastric cancer test. Many of these genes are also associated with an increased risk of other cancer types.
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.
APC BMPR1A CDH1 CTNNA1 EPCAM KIT MLH1 MSH2 MSH6 NF1 PDGFRA PMS2 SDHA SDHB SDHC SDHD SMAD4 STK11 TP53
APC BMPR1A CDH1 CTNNA1 EPCAM KIT MLH1 MSH2 MSH6 NF1 PDGFRA PMS2 SDHA SDHB SDHC SDHD SMAD4 STK11 TP53
These genes can also be ordered as part of broader, cross-cancer, multi-gene panels. Depending on the individual’s clinical and family history, these broader panels may be appropriate and can be ordered at no additional charge.
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. One of the most common causes 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. It is important to note that GISTs are not the same as gastric adenocarcinomas; they differ in their pathology, prognosis, and medical management.
Most cases of gastric cancer are sporadic; however, approximately 3%-5% have a familial component and are due to an identifiable pathogenic variant. The Invitae Gastric Cancer panel tests for:
In individuals with a pathogenic variant in one of these genes, the risk of developing cancer is significantly higher, and many of these cancers may be difficult to detect and/or treat. Identifying those at higher risk may enable additional screening, surveillance, and interventions, which could result in risk-reduction and early diagnosis, thereby increasing the chances of successful treatment and survival.
Individuals with a pathogenic variant in one of these genes 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.
Most of the genes on this panel have autosomal dominant inheritance for hereditary gastric cancer. Some have autosomal recessive inheritance, or result in clinically distinct autosomal recessive conditions, as outlined below:
This panel may be considered for individuals whose personal and/or family history is suggestive of a hereditary gastric cancer syndrome, including:
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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
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 | ||
BMPR1A* | NM_004329.2 | ||
CDH1 | NM_004360.3 | ||
CTNNA1 | NM_001903.3 | ||
EPCAM* | NM_002354.2 | ||
KIT | NM_000222.2 | ||
MLH1* | NM_000249.3 | ||
MSH2* | NM_000251.2 | ||
MSH6 | NM_000179.2 | ||
NF1* | NM_000267.3 | ||
PDGFRA | NM_006206.4 | ||
PMS2 | NM_000535.5 | ||
SDHA* | NM_004168.3 | ||
SDHB | NM_003000.2 | ||
SDHC | NM_003001.3 | ||
SDHD | NM_003002.3 | ||
SMAD4 | NM_005359.5 | ||
STK11 | NM_000455.4 | ||
TP53* | NM_000546.5 |
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.
EPCAM: Analysis is limited to deletion/duplication analysis.
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
NF1: Sequencing analysis for exons 41, 48 includes only cds +/- 10 bp.
SDHA: Deletion/duplication analysis is not offered for this gene. Sequencing analysis for exons 6-8, 14 includes only cds +/- 10 bp.
TP53: Deletion/duplication analysis covers the promoter region.