DPC4 gene in various tumor types.

TLDR

The tissue restriction of alterations in DPC4, as in many other tumor‑suppression genes, underscores the complexity of rate‑limiting checkpoints in human tumorigenesis. We analyzed 338 tumors from 12 anatomic sites for DPC4 alterations, selecting 64 with 18q loss for further sequence analysis. DPC4 inactivation is present in about 48 % of pancreatic carcinomas but occurs in less than 10 % of breast and ovarian cancers, with sequence alterations detected in a minority of these cases.

Abstract

We recently identified a novel tumor-suppressor gene, DPC4, at chromosome 18q21.1 and found that both alleles of DPC4 were inactivated in nearly one-half of the pancreatic carcinomas. Here, we analyzed 338 tumors, originating from 12 distinct anatomic sites, for alterations in the DPC4 gene. Sixty-four specimens were selected for the presence of the allelic loss of 18q and were further analyzed for DPC4 sequence alterations. An alteration of the DPC4 gene sequence was identified in one of eight breast carcinomas and one of eight ovarian carcinomas. These results indicate that whereas DPC4 inactivation is prevalent in pancreatic carcinoma (48%), it is distinctly uncommon (< 10%) in the other tumor types examined. The tissue restriction of alterations in DPC4, as in many other tumor-suppressor genes, emphasizes the complexity of rate-limiting checkpoints in human tumorigenesis.