We recently identified a novel tumor-suppressor gene, DPC4, at chromos
ome 18q21.1 and found that both alleles of DPC4 were inactivated in ne
arly one-half of the pancreatic carcinomas, Here, we analyzed 338 tumo
rs, originating from 12 distinct anatomic sites, for alterations in th
e DPC4 gene, Sixty-four specimens were selected for the presence of th
e allelic loss of 18q and were further analyzed for DPC4 sequence alte
rations, 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 pancr
eatic carcinoma (48%), it is distinctly uncommon (<10%) in the other t
umor types examined, The tissue restriction of alterations in DPC4, as
in many other tumor-suppressor genes, emphasizes the complexity of ra
te-limiting checkpoints in human tumorigenesis.