英國 Wellcome Trust Sanger Institute的科學家，在最新出刊的自然 (Nature)雜志上,，刊載最新的一項研究報告結(jié)果顯示,，該研究團隊的科學家，正進行一項大規(guī)模的基因譯碼計劃,，目標鎖定在 200個特定的腫瘤,，范圍包括 500個特定的目標基因，超過二十五億個基因序列的規(guī)模,。
Sanger Institute 是參與人類基因序列譯碼的重要機構(gòu)之一,，就先前的人類基因序列計劃中，就有超過三分之一的序列,，是透過該研究單位所整合的,，這次該研究單位的目標，鎖定在造成人類疾病的死因中最大比例的腫瘤身上,，就過去相關(guān)研究的了解,，腫瘤的發(fā)生，絕大多數(shù)和基因的變化脫離不了關(guān)系,，不過影響蛋白質(zhì)活動的基因大海茫茫,，沒有一個深入的序列分析，是很難找到這些影響頗大的微小變化,。
這次研究團隊首先鎖定的目標,，是總數(shù)超過 500個激活酵素 (kinase)家族的這類基因,，就過去的了解，統(tǒng)計上引發(fā)最多癌化的基因突變,，就是發(fā)生在參與代謝的各個不同的 kinase身上，研究人員就以 BRAF這個激活酵素的基因為例,，在2002 年的前期研究中統(tǒng)計,，大約超過60% 的腫瘤組織，都可以發(fā)現(xiàn)BRAF kinase 基因變化的證據(jù),，而這次審視的腫瘤范圍,，涵蓋乳癌、肺癌,、直腸癌,、胃癌等，幾乎人類常見的腫瘤都包括進去了,。
相關(guān)的科學家表示將這些癌化的腫瘤 DNA定序出來并不困難,，不過要找出真正啟動癌化的關(guān)鍵基因變化，確實是一個相當具有挑戰(zhàn)性的工作,，希望透過這樣的定序計劃,，可以對未來找到關(guān)鍵的起始基因變化，提供更多可用的線索,。
(資料來源 : Bio.com)
英文原文摘要：
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.
