英国 Wellcome Trust Sanger Institute的科学家，在最新出刊的自然 (Nature)杂志上，刊载最新的一项研究报告结果显示，该研究团队的科学家，正进行一项大规模的基因译码计划，目标锁定在 200个特定的肿瘤，范围包括 500个特定的目标基因，超过二十五亿个基因序列的规模。
Sanger Institute 是参与人类基因序列译码的重要机构之一，就先前的人类基因序列计划中，就有超过三分之一的序列，是透过该研究单位所整合的，这次该研究单位的目标，锁定在造成人类疾病的死因中最大比例的肿瘤身上，就过去相关研究的了解，肿瘤的发生，绝大多数和基因的变化脱离不了关系，不过影响蛋白质活动的基因大海茫茫，没有一个深入的序列分析，是很难找到这些影响颇大的微小变化。
这次研究团队首先锁定的目标，是总数超过 500个激活酵素 (kinase)家族的这类基因，就过去的了解，统计上引发最多癌化的基因突变，就是发生在参与代谢的各个不同的 kinase身上，研究人员就以 BRAF这个激活酵素的基因为例，在2002 年的前期研究中统计，大约超过60% 的肿瘤组织，都可以发现BRAF kinase 基因变化的证据，而这次审视的肿瘤范围，涵盖乳癌、肺癌、直肠癌、胃癌等，几乎人类常见的肿瘤都包括进去了。
相关的科学家表示将这些癌化的肿瘤 DNA定序出来并不困难，不过要找出真正启动癌化的关键基因变化，确实是一个相当具有挑战性的工作，希望透过这样的定序计划，可以对未来找到关键的起始基因变化，提供更多可用的线索。
(资料来源 : 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: 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.
