Mutational Heterogeneity among Individual Tumors in a Case of Multiple Primary Malignancy of the Colon

Abstract

c-Ki-ras mutations were analyzed from quintuple colon tumors in a 75-year-old patient with no family history of colon cancer. Polymerase chain reaction-amplified DNA was sequenced for mutations in c-Ki-ras exon 1. Detected mutations were confirmed with allele-specific PCR which amplified only mutant sequences. Five tumors were histopathologically diagnosed as: adenoma with moderate atypia, adenoma with moderate atypia bearing a focal cancer, adenoma with severe atypia bearing a focal cancer, intramucosal carcinoma, well differentiated adenocarcinoma (advanced). Transitions, G-A, were found at the second base of codon 12 for the adenoma with severe atypia bearing a focal cancer and for the well- differentiated adenocarcinoma. The same substitution was found at the second base of codon 13 in the adenoma with mild atypia bearing a focal cancer. No base substitution at codon 12 or 13 was found for the intramucosal carcinoma nor for the adenoma with moderate atypia. These findings demonstrated there to be heterogeneous genetic and histopathological alterations in the individual tumors of the present case of synchronous malignancy of the colon.