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Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142 [M. W. B., R. A. W., W. C. H.]; Molecular Cytogenetics Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20815 [D. Z., N. P.]; Department of Adult Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts 02115 [W. C. H.]; and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 [R. A. W.]
The majority of adult human epithelial cancers exhibit evidence of genetic instability, and it is widely believed that the genetic instability manifested by aneuploidy or microsatellite instability plays an essential role in the genesis of these tumors. Indeed, most experimental models of cancer also show evidence of genomic instability. The resulting genetic chaos, which has widespread effects on many genes throughout the genome, confounds attempts to determine the precise cohort of genetic changes that are required for the transformation of normal human cells to a tumorigenic state. Here we show that genetic transformation of human kidney epithelial cells can occur in the absence of extensive aneuploidy, chromosomal translocations, and microsatellite instability. These observations demonstrate that the in vitro oncogenic transformation of human cells can proceed without widespread genomic instability.
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