Initial genome sequencing and analysis of multiple myeloma.
Initial genome sequencing and analysis of multiple myeloma.
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多发性骨髓瘤的初始基因组测序和分析。
DOI：
10.1038/nature09837
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发表时间：
2011-03-24
期刊：
影响因子：
64.8
通讯作者：
Golub, Todd R.
中科院分区：
文献类型：
--
作者：
Chapman, Michael A.;Lawrence, Michael S.;Keats, Jonathan J.;Cibulskis, Kristian;Sougnez, Carrie;Schinzel, Anna C.;Harview, Christina L.;Brunet, Jean-Philippe;Ahmann, Gregory J.;Adli, Mazhar;Anderson, Kenneth C.;Ardlie, Kristin G.;Auclair, Daniel;Baker, Angela;Bergsagel, P. Leif;Bernstein, Bradley E.;Drier, Yotam;Fonseca, Rafael;Gabriel, Stacey B.;Hofmeister, Craig C.;Jagannath, Sundar;Jakubowiak, Andrzej J.;Krishnan, Amrita;Levy, Joan;Liefeld, Ted;Lonial, Sagar;Mahan, Scott;Mfuko, Bunmi;Monti, Stefano;Perkins, Louise M.;Onofrio, Robb;Pugh, Trevor J.;Rajkumar, S. Vincent;Ramos, Alex H.;Siegel, David S.;Sivachenko, Andrey;Stewart, A. Keith;Trudel, Suzanne;Vij, Ravi;Voet, Douglas;Winckler, Wendy;Zimmerman, Todd;Carpten, John;Trent, Jeff;Hahn, William C.;Garraway, Levi A.;Meyerson, Matthew;Lander, Eric S.;Getz, Gad;Golub, Todd R.
多发性骨髓瘤是一种无法治愈的浆细胞恶性肿瘤，其发病机制尚不清楚。在这里，我们报告了 38 个肿瘤基因组的大规模并行测序以及它们与匹配的正常 DNA 的比较。整个数据集中的体细胞突变模式提示了几种新的和意想不到的致癌机制。这些包括与蛋白质翻译有关的基因突变（在近一半的患者中可见）、与组蛋白甲基化有关的基因以及与凝血有关的基因。此外，NF-κB 通路 11 个成员的突变表明 NF-κB 信号传导的作用比预期更广泛。具有潜在直接临床意义的是，在 4% 的患者中观察到了激酶 BRAF 的激活突变，这表明在多发性骨髓瘤临床试验中对 BRAF 抑制剂进行了评估。这些结果表明，对大量样本进行癌症基因组测序将产生现有知识无法预料的关于癌症的新见解。
Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumor genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the dataset. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signaling was suggested by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.
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64.8
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