No SMAD4 hypermethylation in colorectal cancer

The chromosome region 18q21 is frequently deleted in colorectal cancers. Th ree candidate tumour suppressor genes, DCC, SMAD4 and SMAD2, map to this re gion. The SMAD4(DPC4) gene was recently identified as a candidate pancreati c cancer suppressor gene. It is also a gene for juvenile polyposis tumour p redisposition syndrome. Somatic SMAD4 mutations have been detected in some colorectal carcinomas. However, the frequency of these mutations is relativ ely low, and whether SMAD4 plays a key role in colorectal tumorigenesis is still unclear. In addition to loss of chromosomal material and intragenic m utations there is a third mechanism, DNA methylation, which may have an imp ortant role in gene inactivation. In the present study, we examined whether promoter hypermethylation could be a mechanism for SMAD4 inactivation. In total, 42 colorectal tumours were selected for the methylation analysis and no evidence of promoter hypermethylation was found. Our result suggests th at hypermethylation of the SMAD4 promoter region is not a frequent event in colorectal tumorigenesis. (C) 2000 Cancer Research Campaign.