Genetic alterations in a patient with Turcot's syndrome

Turcot's syndrome (TS) is a rare disorder associated with the development of both brain and colon neoplasms. Because of the very low incidence of the disease, its molecular basis remains unclear. Presented is a TS case of a 30-year-old Japanese male with a histopathologically confirmed diagnosis of both brain tumor (glioblastoma multiforme) and colon tumor (well-differentiated adenocarcinoma). Germline mutations of the p53 gene, somatic mutations of the Ki-ras, p53 and APC genes, and microsatellite instability (MSI) was examined using polymerase chain reaction (PCR)-single strand conformation polymorphism analysis, followed by PCR-direct sequencing, and sequencing after subcloning. No germline mutations of the p53 gene were found. Somatic mutations of Ki-ras and APC genes were found in the colon adenocarcinoma but not in the brain tumor. No somatic mutation of the p53 gene was present in either colon or brain tumors. Microsatellite instability of both colon and brain tumors was positive in two of four loci. These results indicate that the colon tumor of the TS patient carries the Ki-ras and APC gene mutations. The finding of MSI in both the brain and the colon tumors may support the hypothesis that alterations of DNA repair genes are involved in the tumor development of the TS patient.