美國科學(xué)家近日首次成功測序了一個癌癥患者的基因組,，這一開創(chuàng)性工作為利用新方法揭開癌癥的遺傳學(xué)基礎(chǔ)創(chuàng)造了條件。相關(guān)論文發(fā)表在11月6日的《自然》（Nature）雜志上,。
測序的基因組來自于一位女性,，50多歲死于急性骨髓性白血病（AML）,。美國華盛頓大學(xué)的研究人員利用來自皮膚樣本的遺傳材料,，測序了她2套染色體的DNA，同時根據(jù)骨髓樣本檢測了其腫瘤細(xì)胞中的遺傳突變,。所有樣本均采自患者接受癌癥治療前,，以防DNA受到進(jìn)一步損傷。
隨后,，研究人員將患者的腫瘤基因組與其正?；蚪M進(jìn)行了比較，以期發(fā)現(xiàn)遺傳差異。在患者腫瘤基因組中接近270萬個單核苷變異中,，將近98%同樣也在患者皮膚樣本的DNA中檢測到,，這就大大縮小了進(jìn)一步篩選的范圍。
研究人員最終在患者的腫瘤DNA中僅發(fā)現(xiàn)了10個可能與AML有關(guān)的遺傳突變,，其中8個很罕見,，它們所處基因之前從未被認(rèn)為與AML有關(guān)。研究人員還顯示,，腫瘤樣本中的每個細(xì)胞擁有9個突變,，而且較少發(fā)生的那個突變可能是最后形成的。研究人員懷疑,，所有這些突變對于患者的癌癥都很重要,。
美國國立人類基因組研究所前任主管Francis Collins說：“首次確定人類癌癥基因組的完全DNA序列，并與同一個體的正常組織相比較,，這在癌癥研究中是一個真正的里程碑,。”
美國俄勒岡健康與科學(xué)大學(xué)癌癥研究所的Brian Druker說：“雖然這一研究尚不能告訴我們怎樣治療癌癥患者，但它是這條路上關(guān)鍵的第一步,。它為大規(guī)模癌癥基因組測序和揭示癌癥秘密打下了基礎(chǔ),。”
目前，研究小組正在測序其他AML患者的基因組,，同時他們還計劃將這種全基因組方法擴展到乳腺癌和肺癌,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature，456, 66-72,，Timothy J. Ley,，Richard K. Wilson
DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome
Timothy J. Ley1,2,3,4,9, Elaine R. Mardis2,3,9, Li Ding2,3, Bob Fulton3, Michael D. McLellan3, Ken Chen3, David Dooling3, Brian H. Dunford-Shore3, Sean McGrath3, Matthew Hickenbotham3, Lisa Cook3, Rachel Abbott3, David E. Larson3, Dan C. Koboldt3, Craig Pohl3, Scott Smith3, Amy Hawkins3, Scott Abbott3, Devin Locke3, LaDeana W. Hillier3,8, Tracie Miner3, Lucinda Fulton3, Vincent Magrini2,3, Todd Wylie3, Jarret Glasscock3, Joshua Conyers3, Nathan Sander3, Xiaoqi Shi3, John R. Osborne3, Patrick Minx3, David Gordon8, Asif Chinwalla3, Yu Zhao1, Rhonda E. Ries1, Jacqueline E. Payton5, Peter Westervelt1,4, Michael H. Tomasson1,4, Mark Watson3,4,5, Jack Baty6, Jennifer Ivanovich4,7, Sharon Heath1,4, William D. Shannon1,4, Rakesh Nagarajan4,5, Matthew J. Walter1,4, Daniel C. Link1,4, Timothy A. Graubert1,4, John F. DiPersio1,4 & Richard K. Wilson2,3,4
1 Department of Medicine,
2 Department of Genetics,
3 The Genome Center at Washington University,
4 Siteman Cancer Center,
5 Department of Pathology and Immunology,
6 Division of Biostatistics, and,
7 Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63108, USA
8 Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
9 These authors contributed equally to this work.
Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.
