COMPARATIVE MUTATIONAL ANALYSIS OF DPC4 (SMAD4) IN PROSTATIC AND COLORECTAL CARCINOMAS

Allelic deletions of chromosome 18q are reported to be common in prost ate and colorectal cancers, suggesting that one or more tumor suppress or genes on 18q are involved in the genesis of these neoplasms, The DP C4 gene, a recently identified candidate tumor suppressor in 18q21, wa s examined for evidence of inactivation in prostatic carcinomas, and r esults compared to those of a parallel analysis of colorectal carcinom as, for which DPC4 mutation has been reported in similar to 10% of cas es, In this study, only three (10%) of 29 informative primary prostate cancers showed allelic loss of chromosome 18q21 markers, and no point mutations or deletions of DPC4 were detected in the complete set of 4 5 primary or metastatic cases, In contrast, five (56%) of nine primary colorectal tumors displayed allelic loss of 18q markers and in one of these a somatically acquired G-->T missense mutation was found in exo n 1. Of twelve colorectal tumor cell lines, one showed a G-->C missens e mutation in exon 8 and two had partial homozygous deletions that wou ld likely abrogate gene function, These data suggest that DPC4 is rare ly if ever mutated during prostatic oncogenesis, whereas inactivation of this gene may contribute to the genesis of a subset of colorectal c arcinomas.