DELETION AND MUTATION ANALYSES OF THE P16 MTS-1 TUMOR-SUPPRESSOR GENEIN HUMAN DUCTAL PANCREATIC-CANCER REVEALS A HIGHER FREQUENCY OF ABNORMALITIES IN TUMOR-DERIVED CELL-LINES THAN IN PRIMARY DUCTAL ADENOCARCINOMAS/

The putative tumor suppressor gene p16/CDKN2 encodes a specific inhibi tor of cyclin D-cyclin-dependent kinase 4 completes important in cell- cycle regulation and has been found to be deleted or mutated in a vari ety of human cancers, Thirty microdissected primary human ductal pancr eatic carcinomas from patients not subject to radiotherapy or chemothe rapy prior to surgical resection of their carcinomas and 18 human panc reatic carcinoma cell lines were analyzed by single-strand conformatio n polymorphism (SSCP) and DNA sequence analyses and PCR-based deletion analyses for mutations and homozygous deletions of the p16/CDKN2 gene , respectively, Homozygous deletions of the gene were found in five ce ll lines, and nonpolymorphic SSCP and DNA sequence alterations were fo und within exon 1 in four cell lines and exon 2 in three lines, for an overall frequency of deletions and mutations of 66%, In contrast, hom ozygous deletions of p16/CDKN2 were observed in three primary pancreat ic carcinomas, and five primary tumors revealed SSCP and/or sequence a bnormalities in exon 1 (one case) and exon 2 (four cases), a mutation and deletion frequency of 27%, Immunoblotting analyses confirmed the a bsence of p16/MTS-1 expression in actively proliferating cell Lines wi th a homozygous deletion of the gene and low-to-moderate levels of p16 /MTS-1 expression in cell lines possessing a normal RB-1 gene or prote in, These findings suggest that, although p16/CDKN2 may play a role in the pathobiology of pancreatic dancer, inactivation of this putative tumor suppressor gene occurs more frequently in cell lines than in pri mary ductal pancreatic carcinomas.