Invitae Gastric Cancer Panel


Test description

The Invitae Gastric Cancer Panel analyzes genes that are 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.

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Primary panel (18 genes)


APC: Deletion/duplication analysis covers the 1A and 1B promoter regions.
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).
SDHA: Analysis is limited to sequencing analysis. No clinically-relevant del/dups have been reported.
TP53: Deletion/duplication analysis covers the promoter region.

Add-on preliminary-evidence gene (1 gene)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future. This gene can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


Alternative tests to consider

These genes can also be ordered as part of a broader, cross-cancer, multi-gene panel. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional charge.

  • Familial adenomatous polyposis (FAP)
  • Familial gastrointestinal stromal tumor (GIST)
  • Hereditary diffuse gastric cancer syndrome (HDGC)
  • Hereditary paragangliomas and pheochromocytomas (PGL/PCC)
  • Juvenile polyposis syndrome (JPS)
  • Li-Fraumeni syndrome (LFS)
  • Lynch syndrome
  • Neurofibromatosis type 1 (NF1)
  • Peutz-Jeghers syndrome (JPS)

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. 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:

  • hereditary conditions associated with intestinal-type gastric adenocarcinomas such as Lynch and Peutz-Jeghers syndromes
  • hereditary diffuse gastric cancer syndrome due to pathogenic variants in CDH1, a gene that is associated with diffuse-type adenocarcinomas
  • familial GIST, which is associated with a subset of genes

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 can present differently, even among family members. 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 gastric cancer. Several of these genes also result in clinically distinct autosomal recessive conditions:

  • MLH1, MSH2, MSH6, and PMS2 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).

This panel may be considered for individuals whose personal and/or family history is suggestive of a hereditary gastric cancer syndrome, including:

  • gastric cancer, particularly if early-onset
  • gastric cancer in multiple relatives on the same side of the family
  • gastric and breast cancer (particularly lobular type) in the same individual or family
  • gastric and other GI tumors in one individual or family
  • gastric polyposis

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., breast cancer in a man)

  1. Aarnio, M. Clinicopathological features and management of cancers in lynch syndrome. Patholog Res Int. 2012; 2012:350309. doi: 10.1155/2012/350309. PMID: 22619739
  2. American Cancer Society, Lifetime Risks of Developing Various Cancers. Accessed June 2015.
  3. Antonescu, CR. Gastrointestinal stromal tumor (GIST) pathogenesis, familial GIST, and animal models. Semin Diagn Pathol. 2006; 23(2):63-9. doi: 10.1053/j.semdp.2006.08.003. PMID: 17193819
  4. Bianchi, LK, et al. Fundic gland polyp dysplasia is common in familial adenomatous polyposis. Clin. Gastroenterol. Hepatol. 2008; 6(2):180-5. doi: 10.1016/j.cgh.2007.11.018. PMID: 18237868
  5. Chompret, A, et al. PDGFRA germline mutation in a family with multiple cases of gastrointestinal stromal tumor. Gastroenterology. 2004; 126(1):318-21. doi: 10.1053/j.gastro.2003.10.079. PMID: 14699510
  6. Dwight, T, et al. Familial SDHA mutation associated with pituitary adenoma and pheochromocytoma/paraganglioma. J. Clin. Endocrinol. Metab. 2013; 98(6):E1103-8. doi: 10.1210/jc.2013-1400. PMID: 23633203
  7. Fitzgerald, RC, et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J. Med. Genet. 2010; 47(7):436-44. doi: 10.1136/jmg.2009.074237. PMID: 20591882
  8. Giardiello, FM, et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer. Am. J. Gastroenterol. 2014; 109(8):1159-79. doi: 10.1038/ajg.2014.186. PMID: 25070057
  9. Gill, AJ. Succinate dehydrogenase (SDH) and mitochondrial driven neoplasia. Pathology. 2012; 44(4):285-92. doi: 10.1097/PAT.0b013e3283539932. PMID: 22544211
  10. Goodenberger, ML, et al. PMS2 monoallelic mutation carriers: the known unknown. Genet. Med. 2015; :None. doi: 10.1038/gim.2015.27. PMID: 25856668
  11. Gorgel, A, et al. Coexistence of gastrointestinal stromal tumors (GISTs) and pheochromocytoma in three cases of neurofibromatosis type 1 (NF1) with a review of the literature. Intern. Med. 2014; 53(16):1783-9. doi: 10.2169/internalmedicine.53.2012. PMID: 25130111
  12. Italiano, A, et al. SDHA loss of function mutations in a subset of young adult wild-type gastrointestinal stromal tumors. BMC Cancer. 2012; 12:408. doi: 10.1186/1471-2407-12-408. PMID: 22974104
  13. Janeway, KA, et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc. Natl. Acad. Sci. U.S.A. 2011; 108(1):314-8. doi: 10.1073/pnas.1009199108. PMID: 21173220
  14. Kleinbaum, EP, et al. Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor. Int. J. Cancer. 2008; 122(3):711-8. doi: 10.1002/ijc.23137. PMID: 17943734
  15. Kohlmann, W, Gruber, SB. Lynch Syndrome. 2004 Feb 05. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301390
  16. Lodish, MB, Stratakis, CA. Endocrine tumours in neurofibromatosis type 1, tuberous sclerosis and related syndromes. Best Pract. Res. Clin. Endocrinol. Metab. 2010; 24(3):439-49. doi: 10.1016/j.beem.2010.02.002. PMID: 20833335
  17. Masciari, S, et al. Gastric cancer in individuals with Li-Fraumeni syndrome. Genet. Med. 2011; 13(7):651-7. doi: 10.1097/GIM.0b013e31821628b6. PMID: 21552135
  18. McWhinney, SR, et al. Familial gastrointestinal stromal tumors and germ-line mutations. N. Engl. J. Med. 2007; 357(10):1054-6. doi: 10.1056/NEJMc071191. PMID: 17804857
  19. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Gastric Cancer. Accessed September 2015.
  20. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Breast and Ovarian. Accessed September 2015.
  21. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Colorectal. Accessed September 2015.
  22. Olivier, M, et al. Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res. 2003; 63(20):6643-50. PMID: 14583457
  23. Pantaleo, MA, et al. Analysis of all subunits, SDHA, SDHB, SDHC, SDHD, of the succinate dehydrogenase complex in KIT/PDGFRA wild-type GIST. Eur. J. Hum. Genet. 2014; 22(1):32-9. doi: 10.1038/ejhg.2013.80. PMID: 23612575
  24. Pasini, B, et al. Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur. J. Hum. Genet. 2008; 16(1):79-88. doi: 10.1038/sj.ejhg.5201904. PMID: 17667967
  25. Pharoah, PD, et al. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology. 2001; 121(6):1348-53. doi: 10.1053/gast.2001.29611. PMID: 11729114
  26. Pollock, J, Welsh, JS. Clinical cancer genetics: Part I: Gastrointestinal. Am. J. Clin. Oncol. 2011; 34(3):332-6. doi: 10.1097/COC.0b013e3181dea432. PMID: 20859198
  27. Postow, MA, Robson, ME. Inherited gastrointestinal stromal tumor syndromes: mutations, clinical features, and therapeutic implications. Clin Sarcoma Res. 2012; 2(1):16. doi: 10.1186/2045-3329-2-16. PMID: 23036227
  28. Ricci, R, et al. PDGFRA-mutant syndrome. Mod. Pathol. 2015; 28(7):954-64. doi: 10.1038/modpathol.2015.56. PMID: 25975287
  29. Schulte, KM, et al. Genetics and the clinical approach to paragangliomas. Horm. Metab. Res. 2014; 46(13):964-73. doi: 10.1055/s-0034-1383581. PMID: 25014332
  30. Spigelman, AD, et al. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989; 2(8666):783-5. doi: 10.1016/s0140-6736(89)90840-4. PMID: 2571019
  31. Stratakis, CA, Carney, JA. The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications. J. Intern. Med. 2009; 266(1):43-52. doi: 10.1111/j.1365-2796.2009.02110.x. PMID: 19522824
  32. de, Raedt, T, et al. Intestinal neurofibromatosis is a subtype of familial GIST and results from a dominant activating mutation in PDGFRA. Gastroenterology. 2006; 131(6):1907-12. doi: 10.1053/j.gastro.2006.07.002. PMID: 17087943
  33. van, Lier, MG, et al. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am. J. Gastroenterol. 2010; 105(6):1258-64; author reply 1265. doi: 10.1038/ajg.2009.725. PMID: 20051941
  34. van, der, Post, RS, et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J. Med. Genet. 2015; 52(6):361-74. doi: 10.1136/jmedgenet-2015-103094. PMID: 25979631

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
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: Deletion/duplication analysis covers the 1A and 1B promoter regions.
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).
SDHA: Analysis is limited to sequencing analysis. No clinically-relevant del/dups have been reported.
TP53: Deletion/duplication analysis covers the promoter region.