Pan-urologic cancer genomic subtypes that transcend tissue of origin.
Pan-urologic cancer genomic subtypes that transcend tissue of origin.
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DOI：
10.1038/s41467-017-00289-x
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发表时间：
2017-08-04
影响因子：
16.6
通讯作者：
Creighton CJ
中科院分区：
文献类型：
--
作者：
Chen F;Zhang Y;Bossé D;Lalani AA;Hakimi AA;Hsieh JJ;Choueiri TK;Gibbons DL;Ittmann M;Creighton CJ
泌尿系癌症包括膀胱癌、肾癌、前列腺癌和睾丸癌，其共同分子特征跨越不同类型。在这里，我们表明，1954泌尿系统癌症可以分为9个主要的基因组亚型，在多维和全面的分子表征（包括DNA甲基化和拷贝数，RNA和蛋白质表达）的基础上。首先通过计算去除组织优势效应，以定义这些亚型，这些亚型揭示了共同的过程-部分反映了肿瘤微环境影响-驱动肿瘤谱系中的细胞行为。其中六种亚型的特征是由组织或起源细胞定义的代表性癌症类型的混合物。患者存活率和特异性途径（包括缺氧、代谢、NRF 2-ARE、Hippo和免疫检查点）表现的差异可以进一步区分亚型。巨噬细胞和T细胞浸润的免疫检查点标记物和分子特征在所研究的每种癌症类型的不同子集内相对较高。全泌尿系癌症基因组亚型将促进涉及组织导向域之间的治疗意义的信息共享。泌尿系统癌症具有不同的组织和细胞来源，但具有许多共同的分子特征。在这里，作者使用多维和全面的分子表征将泌尿系统癌症分类为9种主要的基因组亚型，突出了潜在的治疗靶点。
Urologic cancers include cancers of the bladder, kidney, prostate, and testes, with common molecular features spanning different types. Here, we show that 1954 urologic cancers can be classified into nine major genomic subtypes, on the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy number, and RNA and protein expression). Tissue dominant effects are first removed computationally in order to define these subtypes, which reveal common processes—reflecting in part tumor microenvironmental influences—driving cellular behavior across tumor lineages. Six of the subtypes feature a mixture of represented cancer types as defined by tissue or cell of origin. Differences in patient survival and in the manifestation of specific pathways—including hypoxia, metabolism, NRF2-ARE, Hippo, and immune checkpoint—can further distinguish the subtypes. Immune checkpoint markers and molecular signatures of macrophages and T cell infiltrates are relatively high within distinct subsets of each cancer type studied. The pan-urologic cancer genomic subtypes would facilitate information sharing involving therapeutic implications between tissue-oriented domains. Urological cancers have disparate tissues and cells of origin but share many molecular features. Here, the authors use multidimensional and comprehensive molecular characterization to classify urological cancers into nine major genomic subtypes, highlighting potential therapeutic targets.
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DOI：
10.1136/bmj.g4797
发表时间：
2014-11-10
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Jonasch E;Gao J;Rathmell WK
通讯作者：
Rathmell WK
多种致癌途径特征显示人类前列腺肿瘤中的坐标表达模式。
影响因子：
3.7
作者：
Creighton, Chad J.
通讯作者：
Creighton, Chad J.
关于癌症基因组地图集的泛伴奏蛋白质组学观点。
影响因子：
16.6
作者：
Akbani, Rehan;Ng, Patrick Kwok Shing;Werner, Henrica M. J.;Shahmoradgoli, Maria;Zhang, Fan;Ju, Zhenlin;Liu, Wenbin;Yang, Ji-Yeon;Yoshihara, Kosuke;Li, Jun;Ling, Shiyun;Seviour, Elena G.;Ram, Prahlad T.;Minna, John D.;Diao, Lixia;Tong, Pan;Heymach, John V.;Hill, Steven M.;Dondelinger, Frank;Stadler, Nicolas;Byers, Lauren A.;Meric-Bernstam, Funda;Weinstein, John N.;Broom, Bradley M.;Verhaak, Roeland G. W.;Liang, Han;Mukherjee, Sach;Lu, Yiling;Mills, Gordon B.
通讯作者：
Mills, Gordon B.
影响因子：
8
作者：
Chen F;Zhang Y;Parra E;Rodriguez J;Behrens C;Akbani R;Lu Y;Kurie JM;Gibbons DL;Mills GB;Wistuba II;Creighton CJ
通讯作者：
Creighton CJ
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network