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Huang LY , Goodrow TL , Zhang SY , KleinSzanto AJP , Chang H , Ruggeri BA
Deletion and mutation analyses of the P16/MTS-1 tumor suppressor gene in human ductal pancreatic cancer reveals a higher frequency of abnormalities in tumor-derived cell lines than in primary ductal adenocarcinomas
Cancer Research. 1996 Mar 1;56(5) :1137-1141
PMID: ISI:A1996TX17300034   
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Abstract
The putative tumor suppressor gene p16/CDKN2 encodes a specific inhibitor of cyclin D-cyclin-dependent kinase 4 completes 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 chemotherapy prior to surgical resection of their carcinomas and 18 human pancreatic carcinoma cell lines were analyzed by single-strand conformation 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 cell lines, and nonpolymorphic SSCP and DNA sequence alterations were found 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, homozygous deletions of p16/CDKN2 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 absence of p16/MTS-1 expression in actively proliferating cell Lines with 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 protein, 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 primary ductal pancreatic carcinomas.
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Times Cited: 54 English Article TX173 CANCER RES