DPC4 GENE MUTATION IN COLITIS ASSOCIATED NEOPLASIA

Background--Colitis associated dysplasia and cancer often have deletio ns involving the long arm of chromosome 18q, suggesting the location o f a tumour suppressor gene critical for their tumorigenesis. The DPC4 gene, which is genetically inactivated in pancreatic and other cancers , has recently been described. Aim-Because DPC4 is located at 18q21 . 1, the hypothesis that it could be a mutated tumour suppressor gene in colitis associated neoplasms was tested. Patients-Advanced neoplastic lesions from six patients having chronic colitis were analysed for DP C4. Methods-Individual exons of DPC4 were amplified by the polymerase chain reaction (PCR) and sequenced from genomic DNA of tissue specimen s dissected by cryostat. Results-DPC4 was found to have biallelic inac tivation in one of three neoplasms shown to have allelic loss of 18q. The mutation had been acquired somatically in a plaque of high grade d ysplasia. The mutation created a non-sense codon, which would cause pr emature termination of protein translation. Conclusion-The DPC4 gene i s a target of 18q LOH events in colitis associated neoplasia.