Catenin family genes are not commonly mutated in hereditary diffuse gastric cancer.

BACKGROUND Approximately one third of the hereditary diffuse gastric cancer (HDGC) families carry germline mutations in the E-cadherin gene (CDH1). Risk prediction in members of families with this rare but deadly cancer could be improved by the identification of additional HDGC genes in non-CDH1 families. METHODS Affected individuals from 22 CDH1 mutation-negative families were screened for germline mutations in four catenin genes: CTNNA1, CTNNB1, JUP, and CTNND1. Catenins interact closely with E-cadherin molecules in cells, and are therefore logical candidate genes for mutation screening in HDGC families. RESULTS No nonsynonymous variants were seen in CTNNA1, CTNNB1, or CTNND1; only JUP contained nonsynonymous variants, of which only two rare variants were predicted to be deleterious. CONCLUSION Catenin genes are not commonly mutated in non-CDH1 HDGC families. IMPACT Germline mutations in CTNNA1, CTNNB1, JUP, or CTNND1 are unlikely to play a major role in HDGC.