MUTATIONAL HETEROGENEITY AMONG INDIVIDUAL TUMORS IN A CASE OF MULTIPLE PRIMARY MALIGNANCY OF THE COLON

c-Ki-ras mutations were analyzed from quintuple colon tumors in a 75-y ear-old patient with no family history of colon cancer. Polymerase cha in reaction-amplified DNA was sequenced for mutations in c-Ki-ras exon 1. Detected mutations were confirmed with allele-specific PCR which a mplified only mutant sequences. Five tumors were histopathologically d iagnosed as: adenoma with moderate atypia, adenoma with moderate atypi a bearing a focal cancer, adenoma with severe atypia bearing a focal c ancer, intramucosal carcinoma, well differentiated adenocarcinoma (adv anced). Transitions, G-A, were found at the second base of codon 12 fo r the adenoma with severe atypia bearing a focal cancer and for the we ll- 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. Thes e findings demonstrated there to be heterogeneous genetic and histopat hological alterations in the individual tumors of the present case of synchronous malignancy of the colon.