英国Wellcome Trust Sanger Institute进行了一项癌症基因组计划的最新结果显示，驱动癌症形成的突变基因要比之前估计的多。
这项研究的结果刊登在3月的《自然》杂志上，研究还表明每种细胞类型都携带许多其他“旅客”突变。
研究人员测序了超过2.5亿个DNA编码字符，其中包括超过500个基因和200多种癌症——包括结肠癌、胃癌、乳腺癌和肺癌。
研究中还发现原来被认为不可能导致癌症的一些激酶蛋白也是癌症的驱动者。Sanger的研究人员发现癌症突变可以被分为两个组——“驱动者”和“旅客”。
研究人员确定出的120个驱动突变能够促进癌细胞的生长，而“旅客”突变则是伴随的旅行者，不会对癌细胞的生长有影响。
癌症基因组计划的领导人之一Andy Futreal表示，很明显，癌症里的大多数突变都是“旅客”。但是由于他们发现了比之前预测的更多的驱动突变，因此Sanger研究表明有比想象中更多的基因促进癌症的发生。
部分英文原文：
Nature 446, 153-158 (8 March 2007) | doi:10.1038/nature05610; Received 7 September 2006; Accepted 18 January 2007
Patterns of somatic mutation in human cancer genomes
Christopher Greenman1, Philip Stephens1, Raffaella Smith1, Gillian L. Dalgliesh1, Christopher Hunter1, Graham Bignell1, Helen Davies1, Jon Teague1, Adam Butler1, Claire Stevens1, Sarah Edkins1, Sarah O'Meara1, Imre Vastrik2, Esther E. Schmidt2, Tim Avis1, Syd Barthorpe1, Gurpreet Bhamra1, Gemma Buck1, Bhudipa Choudhury1, Jody Clements1, Jennifer Cole1, Ed Dicks1, Simon Forbes1, Kris Gray1, Kelly Halliday1, Rachel Harrison1, Katy Hills1, Jon Hinton1, Andy Jenkinson1, David Jones1, Andy Menzies1, Tatiana Mironenko1, Janet Perry1, Keiran Raine1, Dave Richardson1, Rebecca Shepherd1, Alexandra Small1, Calli Tofts1, Jennifer Varian1, Tony Webb1, Sofie West1, Sara Widaa1, Andy Yates1, Daniel P. Cahill3, David N. Louis3, Peter Goldstraw4, Andrew G. Nicholson4, Francis Brasseur5, Leendert Looijenga6, Barbara L. Weber7, Yoke-Eng Chiew8, Anna deFazio8, Mel F. Greaves9, Anthony R. Green10, Peter Campbell1, Ewan Birney2, Douglas F. Easton11, Georgia Chenevix-Trench12, Min-Han Tan13, Sok Kean Khoo13, Bin Tean Teh13, Siu Tsan Yuen14, Suet Yi Leung14, Richard Wooster1, P. Andrew Futreal1 and Michael R. Stratton1,9
Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
Molecular Pathology Unit, Neurosurgical Service and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
Royal Brompton Hospital, London SW3 6NP, UK
Ludwig Institute for Cancer Research, 1200 Brussels, Belgium
Laboratory of Pathology/Experimental Patho-Oncology, Erasmus MC University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Josephine Nefkens Institute, 3000 DR Rotterdam, UCL 745, B-1200, The Netherlands
University of Pennsylvania Cancer Centre, Philadelphia, Pennsylvania 19104-6160, USA
Department of Gynaecological Oncology, Westmead Hospital and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead NSW 2145, Australia
Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
Department of Haematology, Addenbrooke's NHS Trust and University of Cambridge, Cambridge CB2 0QQ, UK
Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge CB1 8RN, UK
Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Queensland 4029, Australia
Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong
Correspondence to: P. Andrew Futreal1Michael R. Stratton1,9 Correspondence and requests for materials should be addressed to P.A.F. (Email: paf@sanger.ac.uk) or M.R.S. (Email: mrs@sanger.ac.uk).
Abstract
Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.
