Cancer’s Mutational Landscape

The genomes of human tumors contain many sequence alterations, a subset of which help drive tumor growth. Wood et al . (see Perspective by Trent and Touchman) have now undertaken a systematic sequence analysis of >18,000 genes in human breast and colorectal tumors. Depiction of the mutational data on a topographic map indicates that each of these tumor types contains only a few gene "mountains" mutated at high frequency and a much larger number of gene "hills" mutated at low frequency. Importantly, while a large fraction of the mutations driving tumor growth reside in the gene hills rather than the mountains--a finding that underscores the heterogeneity of human cancer--it appears that many of the mutated genes function through cellular signaling pathways that are already well known. L. D. Wood, D. W. Parsons, S. Jones, J. Lin, T. Sjöblom, R. J. Leary, D. Shen, S. M. Boca, T. Barber, J. Ptak, N. Silliman, S. Szabo, Z. Dezso, V. Ustyanksky, T. Nikolskaya, Y. Nikolsky, R. Karchin, P. A. Wilson, J. S. Kaminker, Z. Zhang, R. Croshaw, J. Willis, D. Dawson, M. Shipitsin, J. K. V. Willson, S. Sukumar, K. Polyak, B. H. Park, C. L. Pethiyagoda, P. V. Krishna Pant, D. G. Ballinger, A. B. Sparks, J. Hartigan, D. R. Smith, E. Suh, N. Papadopoulos, P. Buckhaults, S. D. Markowitz, G. Parmigiani, K. W. Kinzler, V. E. Velculescu, B. Vogelstein, The genomic landscapes of human breast and colorectal cancers. Science 318 , 1108-1113 (2007). [Abstract] [Full Text] J. M. Trent, J. W. Touchman, The gene topography of cancer. Science 318 , 1079-1080 (2007). [Summary] [Full Text]