Clinical spectrum and pleiotropic nature of CDH1 germline mutations.

Abstract

CDH1 encodes E-cadherin, a key protein in adherens junctions. Given that E-cadherin is involved in major cellular processes such as embryogenesis and maintenance of tissue architecture, it is no surprise that deleterious effects arise from its loss of function. E-cadherin is recognised as a tumour suppressor gene, and it is well established that CDH1 genetic alterations cause diffuse gastric cancer and lobular breast cancer-the foremost manifestations of the hereditary diffuse gastric cancer syndrome. However, in the last decade, evidence has emerged demonstrating that CDH1 mutations can be associated with lobular breast cancer and/or several congenital abnormalities, without any personal or family history of diffuse gastric cancer. To date, no genotype-phenotype correlations have been observed. Remarkably, there are reports of mutations affecting the same nucleotide but inducing distinct clinical outcomes. In this review, we bring together a comprehensive analysis of CDH1-associated disorders and germline alterations found in each trait, providing important insights into the biological mechanisms underlying E-cadherin's pleiotropic effects. Ultimately, this knowledge will impact genetic counselling and will be relevant to the assessment of risk of cancer development or congenital malformations in CDH1 mutation carriers.

• Authors: Joana Figueiredo, Soraia Melo, Patrícia Carneiro, Ana Margarida Moreira, Maria Sofia Fernandes, Ana Sofia Ribeiro, Parry Guilford, Joana Paredes, Raquel Seruca
• Journal: Journal of medical genetics (J Med Genet) Vol. 56 Issue 4 Pg. 199-208 (04 2019) ISSN: 1468-6244 [Electronic] England
• PMID: 30661051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Antigens, CD
• CDH1 protein, human
• Cadherins

Topics

• Alleles
• Antigens, CD (genetics)
• Breast Neoplasms (genetics)
• Cadherins (genetics)
• Cell Differentiation (genetics)
• Cell Transformation, Neoplastic
• Cleft Lip (genetics)
• Cleft Palate (genetics)
• Ectropion (genetics)
• Female
• Genetic Association Studies (methods)
• Genetic Predisposition to Disease
• Genotype
• Germ-Line Mutation
• Humans
• Male
• Stomach Neoplasms (genetics)
• Tooth Abnormalities (genetics)