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

Daniel L. Stoler, Neng Chen, Mark Basik, Morton S. Kahlenberg, Miguel A. Rodriguez-Bigas, Nicholas J. Petrelli, Garth R. Anderson

Research output: Contribution to journalArticlepeer-review

323 Scopus citations


Cancer cell genomes contain alterations beyond known etiologic events, but their total number has been unknown at even the order of magnitude level. By sampling colorectal premalignant polyp and carcinoma cell genomes through use of the technique inter-(simple sequence repeat) PCR, we have found genomic alterations to be considerably more abundant than expected, with the mean number of genomic events per carcinoma cell totaling approximately 11,000. Colonic polyps early in the tumor progression pathway showed similar numbers of events. These results indicate that, as with certain hereditary cancer syndromes, genomic destabilization is an early step in sporadic tumor development. Together these results support the model of genomic instability being a cause rather than an effect of malignancy, facilitating vastly accelerated somatic cell evolution, with the observed orderly steps of the colon cancer progression pathway reflecting the consequences of natural selection.

Original languageEnglish (US)
Pages (from-to)15121-15126
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number26
StatePublished - Dec 21 1999
Externally publishedYes

ASJC Scopus subject areas

  • General


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