Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients.
Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients.
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DOI：
10.1038/nm.4333
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发表时间：
2017-06
期刊：
影响因子：
82.9
通讯作者：
Berger MF
中科院分区：
文献类型：
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作者：
Zehir A;Benayed R;Shah RH;Syed A;Middha S;Kim HR;Srinivasan P;Gao J;Chakravarty D;Devlin SM;Hellmann MD;Barron DA;Schram AM;Hameed M;Dogan S;Ross DS;Hechtman JF;DeLair DF;Yao J;Mandelker DL;Cheng DT;Chandramohan R;Mohanty AS;Ptashkin RN;Jayakumaran G;Prasad M;Syed MH;Rema AB;Liu ZY;Nafa K;Borsu L;Sadowska J;Casanova J;Bacares R;Kiecka IJ;Razumova A;Son JB;Stewart L;Baldi T;Mullaney KA;Al-Ahmadie H;Vakiani E;Abeshouse AA;Penson AV;Jonsson P;Camacho N;Chang MT;Won HH;Gross BE;Kundra R;Heins ZJ;Chen HW;Phillips S;Zhang H;Wang J;Ochoa A;Wills J;Eubank M;Thomas SB;Gardos SM;Reales DN;Galle J;Durany R;Cambria R;Abida W;Cercek A;Feldman DR;Gounder MM;Hakimi AA;Harding JJ;Iyer G;Janjigian YY;Jordan EJ;Kelly CM;Lowery MA;Morris LGT;Omuro AM;Raj N;Razavi P;Shoushtari AN;Shukla N;Soumerai TE;Varghese AM;Yaeger R;Coleman J;Bochner B;Riely GJ;Saltz LB;Scher HI;Sabbatini PJ;Robson ME;Klimstra DS;Taylor BS;Baselga J;Schultz N;Hyman DM;Arcila ME;Solit DB;Ladanyi M;Berger MF
肿瘤分子谱分析是精准肿瘤学的基本组成部分，能够识别可靶向治疗的基因和通路的基因组改变。不同组织学定义的肿瘤类型中存在反复的靶向改变，加上分子靶向治疗组合的不断扩大，需要灵活而全面的方法来分析整个癌症谱系中具有临床意义的基因。我们利用综合测定 MSK-IMPACT 建立了大规模前瞻性临床测序计划，通过该计划，我们从超过 10,000 名晚期癌症患者的独特队列中收集了匹配的肿瘤和正常序列数据以及可用的病理和临床注释。利用这些数据，我们确定了临床相关的体细胞突变、新型非编码改变以及常见和罕见肿瘤类型共有的突变特征。患者以 11% 的比例参加基因组匹配临床试验。为了发现新的生物标志物并对罕见的改变和肿瘤类型进行更深入的研究，所有结果都是公开的。
Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The existence of recurrent targetable alterations across distinct histologically-defined tumor types, coupled with an expanding portfolio of molecularly-targeted therapies, demands flexible and comprehensive approaches to profile clinically significant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative utilizing a comprehensive assay, MSK-IMPACT, through which we have compiled matched tumor and normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer and available pathological and clinical annotations. Using these data, we identified clinically relevant somatic mutations, novel non-coding alterations, and mutational signatures that were shared among common and rare tumor types. Patients were enrolled on genomically matched clinical trials at a rate of 11%. To enable discovery of novel biomarkers and deeper investigation into rare alterations and tumor types, all results are publicly accessible.