Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria

摘要: Background: Mutations in the E-cadherin (CDH1) gene are a well documented cause of hereditary diffuse gastric cancer (HDGC). Development evidence based guidelines for CDH1 screening HDGC have been complicated by its rarity, variable penetrance, and lack founder mutations. Methods: Forty three new (GC) families were ascertained from multiple sources. In 42 these at least one was pathologically confirmed to be (DGC); other family had intestinal type cancers. Screening entire coding region all intron/exon boundaries performed bi-directional sequencing. Results: Novel mutations found 13 DGC (31% overall). Twelve occur among 25 with cases pathologic confirmation phenotype individual under age 50 years. The include small insertions deletions, splice site mutations, non-conservative amino acid substitutions (A298T, W409R, R732Q). All missense conferred loss function vitro assays. Multiple breast cancers including lobular observed both mutation positive negative families. Conclusion: Germline truncating 48% case an years age. We recommend that criteria used selecting mutational analysis.