Genetic analysis of multiple synchronous lesions of the colon adenoma-carcinoma sequence

The colorectal adenoma-carcinoma sequence represents a well-known paradigm for the sequential development of cancer driven by the accumulation of geno mic defects. Although the colorectal adenoma-carcinoma sequence is well inv estigated, studies about tumours of different dignity co-existent in the sa me patient are seldom. In order to address the distribution of genetic alte rations in different lesions of the same patient, we coincidently investiga ted carcinomas, adenomas and aberrant crypt foci in patients with sporadic colon cancer. By utilizing polymerase chain reaction, single-strand conform ation polymorphism, heteroduplex-analysis, restriction fragment length poly morphism, protein truncation test and sequencing techniques we looked for m utations and microsatellite instability of APC, H-ras, K-ras, p53, DCC and the DNA repair genes hMLH1/hMSH2, In accordance with the suggested adenoma- carcinoma sequence of the colon, four patients reflected the progressive ac cumulation of genetic defects in synchronously appearing tumours during car cinogenesis, However, two patients with non-hereditary malignomas presented different genetic instabilities in different but synchronously appearing t umours suggesting non-clonal growth under almost identical conditions of th e environment. Thus, sporadically manifesting multiple lesions of the colon were not necessarily driven by similar genetic mechanisms, Premalignant le sions may transform into malignant tumours starting from different types of genetic instability, which indicates independent and simultaneous tumorige nesis within the same organ. (C) 2000 Cancer Research Campaign.