GENOMIC SEQUENCING OF DPC4 IN THE ANALYSIS OF FAMILIAL PANCREATIC-CARCINOMA

A first-degree relative with pancreatic cancer is found in 5% to 10% o f patients with pancreatic carcinomas, suggesting an inherited predisp osition for this neoplasm. The recently identified DPC4 tumor suppress or gene is a strong candidate for the gene responsible for the familia l form of pancreatic carcinoma. DPC4 was identified in a consensus are a of homozygous deletion in pancreatic carcinomas, and it is biallelic ally inactivated in approximately 50% of sporadic pancreatic carcinoma s. The coding sequence of this gene is 1660 nucleotides in length, cov ering 11 exons. We describe optimized primers and conditions used in p olymerase chain reaction and cycle sequencing of the entire DPC4 codin g sequence of 25 individuals (eight with pancreatic carcinoma) from 11 kindreds with a familial aggregation of pancreatic carcinoma. No muta tions in the coding sequences of the DPC4 gene were found; hence, it a ppears that germline mutations in DPC4 cannot account for many of the familial aggregations of pancreatic carcinoma.