Germline mutations of the dpc4 gene in Korean juvenile polyposis patients

Juvenile polyposis is an uncommon condition characterized by the developmen t of multiple (usually more than 5) juvenile polyps in the gastrointestinal tract, especially in the colon. This disease usually occurs during childho od, and is inherited in an autosomal dominant fashion. It has been suggeste d that the dpc4 (deleted in pancreatic carcinoma, locus 4) gene, which is l ocated on chromosome 18q21.1, might cause juvenile polyposis. The dpc4 (sma d4) gene is a candidate tumor-suppressor gene and may play a role in the TG F-beta-signaling pathway. To confirm the idea that alterations of the dpc4 gene may result in juvenile polyposis, we screened 5 Korean juvenile-polypo sis patients by PCR-SSCP (single-strand conformation polymorphism) analysis and bidirectional sequencing. There were germline mutations of the dpc4 ge ne in 3 out of the 5 patients: 2 had a genetic alteration in exon 9 and the third had a mutation in exon 8. These germline mutations occurred in the C -terminus of the dpc4 gene, similar to most published mutations. One patien t exhibited a non-sense mutation (codon 388), which changed a glutamine cod on (CAG) to a stop codon (TAG). The second patient harbored a mis-sense mut ation (codon 390), causing a non-conservative amino-acid change (glutamate (GAA) to lysine (AAA)]. The third patient had a mis-sense mutation in exon 8 (codon 361), which altered an arginine codon (CGC) into a histidine codon (CAC). Int. J. Cancer 86: 529-532, 2000. (C) 2000 Wiley-Liss, Inc.