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 results in an increased risk of both 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)


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 the 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 of gastric cancer is 38 years, with a range of 14 years to 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 orofacial clefts may be a feature of HDGC.

Individuals with a pathogenic CDH1 variant have an increased risk of malignancy compared to the average person, but not everyone with a pathogenic variant will actually develop cancer. Further, HGDC is variable, meaning individuals with the same condition may 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.

The lifetime risk for developing gastric cancer in those with a pathogenic variant in CDH1 is 67-80% for men and 56-83% for women. Women have a 39%-52% risk for lobular breast cancer.

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. American Society of Clinical Oncology, Cancer.Net: Hereditary diffuse gastric cancer. Accessed September 2015.
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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: PMID: 20301318
  7. 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
  8. 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
  9. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Breast and Ovarian. Accessed September 2015.
  10. National Library of Medicine, Genetics Home Reference: CDH1. Accessed June 2015.
  11. 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
  12. 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
  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

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
CDH1 NM_004360.3