The Genomic Landscapes of Human Breast and Colorectal Cancers.by: Laura D D Wood, D Williams W Parsons, Siân Jones, Jimmy Lin, Tobias Sjöblom, Rebecca J J Leary, Dong Shen, Simina M M Boca, Thomas Barber, Janine Ptak, Natalie Silliman, Steve Szabo, Zoltan Dezso, Vadim Ustyanksky, Tatiana Nikolskaya, Yuri Nikolsky, Rachel Karchin, Paul A A Wilson, Joshua S S Kaminker, Zemin Zhang, Randal Croshaw, Joseph Willis, Dawn Dawson, Michail Shipitsin, James K V K Willson, Saraswati Sukumar, Kornelia Polyak, Ben Ho H Park, Charit L L Pethiyagoda, P V Krishna V Pant, Dennis G G Ballinger, Andrew B B Sparks, James Hartigan, Douglas R R Smith, Erick Suh, Nickolas Papadopoulos, Phillip Buckhaults, Sanford D D Markowitz, Giovanni Parmigiani, Kenneth W W Kinzler, Victor E E Velculescu, Bert Vogelstein
Science (11 October 2007)
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AbstractHuman cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalogue the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
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