The 18q21 region in colorectal and pancreatic cancer: independent loss of DCC and DPC4 expression

The 18q21 region is frequently altered in gastrointestinal tumors. Three ca ndidate tumor suppressor genes have been identified in it: DCC, Smad4/DPC4 and Smad2; the mechanisms involving their inactivation have not been comple tely elucidated. In this study, genetic losses at 18q21 and expression of D CC and DPC4 in colorectal (n = 12) a:nd pancreatic (n = 16) cell lines and in colorectal tissues (n = 10) were analyzed. The status of the 18q21 regio n was assessed using microsatellite analysis and duplex PCR of exonic seque nces; expression was analyzed by RT-PCR; mutational analysis of DPC4 cDNA w as performed in selected cases. Homozygous losses of microsatellite markers at 18q21 were not observed in colon or pancreas lines; however, a higher p roportion of apparent homozygosity than expected was found. DCC and DPC4 tr anscripts were detected in 11/12 and 12/12 colorectal cancer lines, respect ively. In tumors, homozygous losses at 18q21 were detected in three cases, without affecting DCC. All tumors retained DCC and DPC4 mRNA expression. In pancreatic lines, DPC4 was inactivated through homozygous deletion (n = 5) , intragenic mutation (n = 3), and lack of protein (n = 2). In conclusion: (1) microsatellite analysis does not provide adequate information regarding homozygous losses at 18q21; (2) approximately 65% of pancreas cancer lines show inactivation of DPC4; and (3) loss of DCC and DPC4 occur independentl y. (C) 2000 Elsevier Science B.V. All rights reserved.