The onset and extent of genomic instability in sporadic colorectal tumor progression

Cancer cell genomes contain alterations beyond known etiologic events, but their total number has been unknown at even the order of magnitude level. B y sampling colorectal premalignant polyp and carcinoma cell genomes through use of the technique inter-(simple sequence repeat) PCR, we have found gen omic alterations to be considerably more abundant than expected, with the m ean number of genomic events per carcinoma cell totaling approximately 11,0 00, Colonic polyps early in the tumor progression pathway showed similar nu mbers of events. These results indicate that, as with certain hereditary ca ncer syndromes, genomic destabilization is an early step in sporadic: tumor development. Together these results support the model of genomic instabili ty being a cause rather than an effect of malignancy, facilitating vastly a ccelerated somatic cell evolution, with the observed orderly steps of the c olon cancer progression pathway reflecting the consequences of natural sele ction.