Genetic Alterations in the Molecular Subtypes of Bladder Cancer: Illustration in the Cancer Genome Atlas Dataset.
Genetic Alterations in the Molecular Subtypes of Bladder Cancer: Illustration in the Cancer Genome Atlas Dataset.
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DOI：
10.1016/j.eururo.2017.03.010
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发表时间：
2017-09
期刊：
影响因子：
23.4
通讯作者：
Lerner SP
中科院分区：
文献类型：
--
作者：
Choi W;Ochoa A;McConkey DJ;Aine M;Höglund M;Kim WY;Real FX;Kiltie AE;Milsom I;Dyrskjøt L;Lerner SP
最近的全基因组mRNA表达谱研究表明，膀胱癌可以分为分子亚型，其中一些亚型与乳腺癌固有亚型和其他实体肿瘤中的分子亚型具有相同的临床特征和基因表达模式。其他实体肿瘤的分子亚型富含特定的突变和拷贝数畸变，这被认为是其独特的进展模式、生物学和临床特性的基础。来自癌症基因组图谱（TCGA）和其他大型项目的全面基因组数据的可用性使得将DNA改变的存在与肿瘤分子亚型成员关系联系起来成为可能。我们的总体目标是确定特定的DNA突变和/或拷贝数变异是否在特定的分子亚型中富集。我们使用完整的TCGA RNA-seq数据集和我们的团队开发的三种不同的已发表分类器将TCGA膀胱癌分配到分子亚型，并检查了其中最常见的DNA改变的流行程度。我们根据已发表的关于这些改变在非肌肉浸润性和肌肉浸润性膀胱癌中普遍存在的文献来解释这些结果。结果证实，涉及RB1和NFE2L2的改变在基底癌中富集，而涉及FGFR3和KDM6A的改变在管腔肿瘤中富集。这些结果进一步强化了膀胱癌分子亚型是具有特定遗传改变的独特疾病实体的结论。我们的观察表明，一些亚型富集突变和拷贝数变异在临床上是可操作的，这对膀胱癌患者的临床管理具有直接意义。
Recent whole genome mRNA expression profiling studies revealed that bladder cancers can be grouped into molecular subtypes, some of which share clinical properties and gene expression patterns with the intrinsic subtypes of breast cancer and the molecular subtypes found in other solid tumors. The molecular subtypes in other solid tumors are enriched with specific mutations and copy number aberrations that are thought to underlie their distinct progression patterns, and biological and clinical properties. The availability of comprehensive genomic data from The Cancer Genome Atlas (TCGA) and other large projects made it possible to correlate the presence of DNA alterations with tumor molecular subtype membership. Our overall goal was to determine whether specific DNA mutations and/or copy number variations are enriched in specific molecular subtypes. We used the complete TCGA RNA-seq dataset and three different published classifiers developed by our groups to assign TCGA’s bladder cancers to molecular subtypes, and examined the prevalence of the most common DNA alterations within them. We interpreted the results against the background of what was known from the published literature about the prevalence of these alterations in nonmuscle-invasive and muscle-invasive bladder cancers. The results confirmed that alterations involving RB1 and NFE2L2 were enriched in basal cancers, whereas alterations involving FGFR3 and KDM6A were enriched in luminal tumors. The results further reinforce the conclusion that the molecular subtypes of bladder cancer are distinct disease entities with specific genetic alterations. Our observation showed that some of subtype-enriched mutations and copy number variations are clinically actionable, which has direct implications for the clinical management of patients with bladder cancer.
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影响因子：
4.6
作者：
Aine M;Eriksson P;Liedberg F;Sjödahl G;Höglund M
通讯作者：
Höglund M
影响因子：
56.9
作者：
Golub, TR;Slonim, DK;Lander, ES
通讯作者：
Lander, ES
影响因子：
23.4
作者：
Allory, Yves;Beukers, Willemien;Real, Francisco X.
通讯作者：
Real, Francisco X.
影响因子：
23.4
作者：
Groenendijk, Floris H.;de Jong, Jeroen;van der Heijden, Michiel S.
通讯作者：
van der Heijden, Michiel S.
DOI：
10.1126/science.1253462
发表时间：
2014-10-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Bruin EC;McGranahan N;Mitter R;Salm M;Wedge DC;Yates L;Jamal-Hanjani M;Shafi S;Murugaesu N;Rowan AJ;Grönroos E;Muhammad MA;Horswell S;Gerlinger M;Varela I;Jones D;Marshall J;Voet T;Van Loo P;Rassl DM;Rintoul RC;Janes SM;Lee SM;Forster M;Ahmad T;Lawrence D;Falzon M;Capitanio A;Harkins TT;Lee CC;Tom W;Teefe E;Chen SC;Begum S;Rabinowitz A;Phillimore B;Spencer-Dene B;Stamp G;Szallasi Z;Matthews N;Stewart A;Campbell P;Swanton C
通讯作者：
Swanton C