Genetic analysis of multiple sporadic colon carcinomas from a single patient

At least two separate genetic pathways of carcinogenesis in sporadic colon cancer involving the accumulation of mutations at various genetic loci have been described. About 15% of sporadic colorectal carcinomas arise via a me chanism associated with microsatellite instability (MSI) and mutations in t ransforming growth factor beta receptor II (TGF beta RII), insulin-like gro wth factor II receptor (IGFIIR) and BAX, whilst the remaining 85% are assoc iated with aneuploidy and gross chromosomal rearrangements. An 81-year-old woman had a sigmoid colon carcinoma resected and is months later developed two additional carcinomas of the caecum and transverse colon. To investigat e whether there was a common genetic mechanism of carcinogenesis for the th ree lesions, MSI status was assessed, TGF beta RII, IGFIIR and BAX were ana lysed for mutations and protein expression of transforming growth factor be ta 1 (TGF beta 1) and p53 were studied using immunohistochemistry. The caec al and transverse colonic carcinomas were both MSI positive but different m utations were identified in each lesion. No genetic abnormalities were iden tified in the sigmoid colonic carcinoma. This suggests that each carcinoma arose via a separate genetic mechanism of carcinogenesis.