DPC4 gene mutation in colitis associated neoplasia

Background - Colitis associated dysplasia and cancer often have deletions involving the long arm of chromosome 18q, suggesting the location of 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 DPC4. Methods - Individual exons of DPC4 were amplified by the polymerase chain reaction (PCR) and sequenced from genomic DNA of tissue specimens dissected by cryostat. Results DPC4 was found to have biallelic inactivation in one of three neoplasms shown to have allelic loss of 18q. The mutation had been acquired somatically in a plaque of high grade dysplasia. The mutation created a non-sense codon, which would cause premature termination of protein translation. Conclusion - The DPC4 gene is a target of 18q LOH events in colitis associated neoplasia.