• Test code: 01707
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Hereditary Diffuse Gastric Cancer Syndrome Test

Test description

This test analyzes the CDH1 gene, which is associated with hereditary diffuse gastric cancer syndrome (HDGC). This condition is also associated with an increased risk of gastric and lobular breast cancer.

Genetic testing of this gene 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.

Order test

Primary panel (1 gene)
Add-on preliminary evidence gene(s) for HDGC (1 gene)

Genes with preliminary evidence of association with hereditary breast cancer are available to add on to the primary panel. Adding on preliminary-evidence genes can increase the number of variants of uncertain significance that are identified. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future.


Alternative tests to consider

HGDC can also be ordered as part of a larger panel to test for different types of hereditary cancer, including breast and colon cancers. Depending on an individual’s clinical and family history, one of these larger panels may be appropriate. Any of these larger panels can be ordered for no additional charge.

  • hereditary diffuse gastric cancer (HGDC)

Hereditary diffuse gastric cancer (HDGC) is an adult-onset hereditary cancer syndrome that increases an individual’s risk of developing diffuse gastric cancer. Diffuse gastric cancer is a type of adenocarcinoma that infiltrates and thickens the stomach wall without forming a distinct tumor mass. Signet ring cells are often observed throughout the stomach wall. Symptoms typically present in advanced disease and can include stomach pain, nausea, vomiting, difficulty swallowing, decreased appetite and weight loss.

Individuals with HDGC have up to an 83% risk of developing diffuse gastric cancer. The average age of onset is 38 years, with a range of 14-69 years. Women with this inherited predisposition also have an approximately 52% risk of developing lobular carcinoma of the breast. There is also evidence to suggest that colon cancer and orofacial clefts may be a feature of HDGC.

Individuals with a pathogenic variant in this gene 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.

Pathogenic variants are identified in 30%-50% of affected individuals. Deletion/duplication analysis identifies an additional 4% of cases.

HDGC is inherited in an autosomal dominant pattern. Most cases are inherited from a parent. Spontaneous de novo mutations are uncommon.

Gastric cancer is the fourth-commonest cancer worldwide, but less than 1% of these cases are due to HDGC.

Testing for CDH1 may be considered for individuals with the following:

  • diffuse gastric cancer before the age of 40 years
  • bilateral or familial lobular breast cancer before the age of 50 years
  • diffuse gastric cancer and cleft lip/palate
  • precursor lesions for signet ring cell carcinoma

Clinical diagnostic criteria for HDGC have been developed by the International Gastric Cancer Linkage Consortium in 2010

  1. Vogelaar, IP, et al. Identification of germline mutations in the cancer predisposing gene CDH1 in patients with orofacial clefts. Hum. Mol. Genet. 2013; 22(5):919-26. doi: 10.1093/hmg/dds497. PMID: 23197654
  2. Kluijt, I, et al. CDH1-related hereditary diffuse gastric cancer syndrome: clinical variations and implications for counseling. Int. J. Cancer. 2012; 131(2):367-76. doi: 10.1002/ijc.26398. PMID: 22020549
  3. Kaurah, P, Huntsman, DG. Hereditary Diffuse Gastric Cancer. 2002 Nov 04. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1139/ PMID: 20301318
  4. Hampel, H, et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet. Med. 2015; 17(1):70-87. doi: 10.1038/gim.2014.147. PMID: 25394175
  5. 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
  6. Frebourg, T, et al. Cleft lip/palate and CDH1/E-cadherin mutations in families with hereditary diffuse gastric cancer. J. Med. Genet. 2006; 43(2):138-42. doi: 10.1136/jmg.2005.031385. PMID: 15831593
  7. National Cancer Institute, Who should consider genetic testing for cancer risk? http://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet#q4 Accessed September 2019.
  8. National Comprehensive Cancer Network®, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Breast and Ovarian Version 3.2019. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp Accessed September 2019
  9. American Society of Clinical Oncology, Cancer.Net. http://www.cancer.net/cancer-types/hereditary-diffuse-gastric-cancer Accessed September 2019.
  10. National Library of Medicine, Genetics Home Reference: CDH1. http://ghr.nlm.nih.gov/gene/CDH1 Accessed September 2019.
  11. National Comprehensive Cancer Network®, Clinical Practice Guidelines in Oncology (NCCN Guidelines): Gastric Cancer Version 2.2019. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp Accessed September 2019.
  12. Majewski, IJ, et al. An α-E-catenin (CTNNA1) mutation in hereditary diffuse gastric cancer. J. Pathol. 2013; 229(4):621-9. doi: 10.1002/path.4152. PMID: 23208944
  13. 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
  14. 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
  15. Kaurah, P, et al. Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA. 2007; 297(21):2360-72. doi: 10.1001/jama.297.21.2360. PMID: 17545690
  16. Hansford, S, et al. Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond. JAMA Oncol. 2015; 1(1):23-32. doi: 10.1001/jamaoncol.2014.168. PMID: 26182300
  17. Benusiglio, PR, et al. Cleft lip, cleft palate, hereditary diffuse gastric cancer and germline mutations in CDH1. Int. J. Cancer. 2013; 132(10):2470. doi: 10.1002/ijc.27923. PMID: 23124477

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. 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
CDH1 NM_004360.3
CTNNA1 NM_001903.3