英國(guó)Wellcome Trust Sanger Institute進(jìn)行了一項(xiàng)癌癥基因組計(jì)劃的最新結(jié)果顯示,，驅(qū)動(dòng)癌癥形成的突變基因要比之前估計(jì)的多,。
這項(xiàng)研究的結(jié)果刊登在3月的《自然》雜志上,，研究還表明每種細(xì)胞類型都攜帶許多其他“旅客”突變,。
研究人員測(cè)序了超過(guò)2.5億個(gè)DNA編碼字符,，其中包括超過(guò)500個(gè)基因和200多種癌癥——包括結(jié)腸癌,、胃癌,、乳腺癌和肺癌,。
研究中還發(fā)現(xiàn)原來(lái)被認(rèn)為不可能導(dǎo)致癌癥的一些激酶蛋白也是癌癥的驅(qū)動(dòng)者。Sanger的研究人員發(fā)現(xiàn)癌癥突變可以被分為兩個(gè)組——“驅(qū)動(dòng)者”和“旅客”,。
研究人員確定出的120個(gè)驅(qū)動(dòng)突變能夠促進(jìn)癌細(xì)胞的生長(zhǎng),，而“旅客”突變則是伴隨的旅行者，不會(huì)對(duì)癌細(xì)胞的生長(zhǎng)有影響,。
癌癥基因組計(jì)劃的領(lǐng)導(dǎo)人之一Andy Futreal表示,，很明顯，癌癥里的大多數(shù)突變都是“旅客”,。但是由于他們發(fā)現(xiàn)了比之前預(yù)測(cè)的更多的驅(qū)動(dòng)突變,，因此Sanger研究表明有比想象中更多的基因促進(jìn)癌癥的發(fā)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: [email protected]) or M.R.S. (Email: [email protected]).
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.
