FREQUENT MUTATIONS OF CDKN2 IN PRIMARY PANCREATIC ADENOCARCINOMAS

The gene encoding the cell-cycle regulatory protein p16, CDKN2, is loc alized on chromosome band 9p21. CDKN2 is frequently deleted or mutated in a variety of tumor cell lines, including pancreatic cancer cell li nes and xenografts, as well as in some primary tumors. We examined 32 primary pancreatic adenocarcinomas for CDKN2 mutations and for loss of heterozygosity of 9p21 sequences to assess the role of CDKN2 in pancr eatic carcinogenesis. Single-strand conformation variant analysis (SSC V) and direct sequencing of the variants revealed somatic CDKN2 mutati ons in 11 of 32 tumors (five frame-shift mutations, five nonsense muta tions, and one missense mutation). One tumor appeared to be characteri zed by homozygous deletion of CDKN2. These results suggest that CDKN2 plays an important role during tumorigenesis or tumor progression in a significant proportion of pancreatic adenocarcinomas. (C) 1995 Wiley- Liss, Inc.