Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer death in men and the fifth leading cause in women in the United States, with nearly coincident incidence and mortality rates

The putative tumor suppressor gene pi6/CDKN2 encodes a specific Inhibitor of cydlin D-cydlln-dependent kinase 4 complexes important in cell-cycle regulation and has been found to be deleted or mutated in a variety of human cancers. Thirty microdissected primary human ductal pancreatic carcinomas from patients not subject to radiotherapy or them otherapy prior to sur@cal resection of their carcinomas and 18 human pancreatic carcinoma cell lines were analyzed by single-strand conforma tion polymorphism (SSCP) and DNA sequence analyses and PCR-based deletion analyses for mutations and homozygous deletions of the pitS! CDKN2 gene, respectively. Homozygous deletions of the gene were found infivecelllines,andnonpolymorphic SSCPandDNAsequencealterations were found within exon 1 in four cell lines and exon 2 in three lines, for an overall frequency ofdeletions and mutations of66%. In contrast, homozy goes deletions ofpi6JCDKN2 were observed in three primary pancreatic carcinomas, and five primary tumors revealed SSCP and/or sequence abnormalities in exon 1 (one case) and exon 2 (four cases), a mutation and deletion frequency of 27%. Immunoblotting analyses confirmed the ab sence of pitS/lifTS-i expression in actively proliferating cell lines with a homozygous deletion ofthe gene and low-to-moderate levels of pi6IMTS-i expression in cell lines possessing a normal RB-i gene or protein. These fluidlngs suggest that, althOUghpi6JCDKN2 may play a role in the patho biology of pancreatic cancer, Inactivation of this putative tumor suppres sor gene occurs more frequently In cell lines than in primary ductal pancreatic carcinomas.