美国科学家近日首次成功测序了一个癌症患者的基因组，这一开创性工作为利用新方法揭开癌症的遗传学基础创造了条件。相关论文发表在11月6日的《自然》（Nature）杂志上。
测序的基因组来自于一位女性，50多岁死于急性骨髓性白血病（AML）。美国华盛顿大学的研究人员利用来自皮肤样本的遗传材料，测序了她2套染色体的DNA，同时根据骨髓样本检测了其肿瘤细胞中的遗传突变。所有样本均采自患者接受癌症治疗前，以防DNA受到进一步损伤。
随后，研究人员将患者的肿瘤基因组与其正常基因组进行了比较，以期发现遗传差异。在患者肿瘤基因组中接近270万个单核苷变异中，将近98%同样也在患者皮肤样本的DNA中检测到，这就大大缩小了进一步筛选的范围。
研究人员最终在患者的肿瘤DNA中仅发现了10个可能与AML有关的遗传突变，其中8个很罕见，它们所处基因之前从未被认为与AML有关。研究人员还显示，肿瘤样本中的每个细胞拥有9个突变，而且较少发生的那个突变可能是最后形成的。研究人员怀疑，所有这些突变对于患者的癌症都很重要。
美国国立人类基因组研究所前任主管Francis Collins说：“首次确定人类癌症基因组的完全DNA序列，并与同一个体的正常组织相比较，这在癌症研究中是一个真正的里程碑。”
美国俄勒冈健康与科学大学癌症研究所的Brian Druker说：“虽然这一研究尚不能告诉我们怎样治疗癌症患者，但它是这条路上关键的第一步。它为大规模癌症基因组测序和揭示癌症秘密打下了基础。”
目前，研究小组正在测序其他AML患者的基因组，同时他们还计划将这种全基因组方法扩展到乳腺癌和肺癌。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
