P53 MUTATIONS IN PANCREATIC-CARCINOMA AND EVIDENCE OF COMMON INVOLVEMENT OF HOMOCOPOLYMER TRACTS IN DNA MICRODELETIONS

Pancreatic adenocarcinoma is a major cause of cancer death, and yet li ttle is known about its molecular pathogenesis. We identified p53 muta tions in 19 (70%) of 27 primary pancreatic adenocarcinomas. Most were missense point mutations, and the mutations were distributed primarily within the evolutionarily conserved domains. Transitions predominated over transversions, and many of the transitions were at CpG dinucleot ides. Intragenic deletions accounted for 32% of mutations and were ass ociated with decreased survival (P = 0.0016). A review of 1937 publish ed p53 mutations revealed that the occurrence of small (1-2 base pairs ) microdeletions varied among different types of human neoplasms and t hat pancreatic adenocarcinoma had one of the highest frequencies (13% of 47 mutations, P = 0.0036). Many small deletions occurred in iterati ons of single bases, but this did not fully account for their pattern of distribution, and there was evidence for the involvement of homocop olymer (polypurine:polypyrimidine) tracts. This may represent a more w idespread phenomenon, because microdeletions occur in similar sequence patterns in reports of somatic and germ line mutations among genes ot her than p53.