Novel germline CDH1 mutations in hereditary diffuse gastric cancer families

✍ Scribed by Bostjan Humar; Tumi Toro; Francesco Graziano; Hansjakob Müller; Zuzana Dobbie; Han Kwang-Yang; Charis Eng; Heather Hampel; Dale Gilbert; Ingrid Winship; Susan Parry; Robyn Ward; Mike Findlay; Alice Christian; Monica Tucker; Kathy Tucker; Tony Merriman; Parry Guilford

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 414 KB
• Volume: 19
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.10067

✦ Synopsis

Hereditary diffuse gastric cancer (HDGC) is a recently defined cancer syndrome caused by inactivating, heterozygous germline mutations in the gene for the cell-to-cell adhesion protein E-cadherin (CDH1). Here, we describe the search for CDH1 mutations in 10 newly identified gastric cancer families. Seven of 10 families met the clinical criteria for HDGC. Germline mutations were identified in four of these seven families and one family that was borderline for the clinical criteria. Of the mutations identified in the five new families, four were previously unreported and consisted of two frameshift and two donor splice site mutations. One splice site mutation occurred at the 100% conserved +1 position. The second splice site mutation occurred at the +5 position and was shown to lead to abnormal splicing. Additional CDH1 variants detected include the heterozygous 160 C®A promoter polymorphism, which has previously been reported to be associated with decreased CDH1 transcription. We, however, found this polymorphism to be common in a control population, suggesting that a major role for this polymorphism in gastric cancer susceptibility is unlikely. Hum Mutat 19:518525, 2002.