Linking Binary Gene Relationships to Drivers of Renal Cell Carcinoma Reveals Convergent Function in Alternate Tumor Progression Paths
Linking Binary Gene Relationships to Drivers of Renal Cell Carcinoma Reveals Convergent Function in Alternate Tumor Progression Paths
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将二元基因关系与肾细胞癌的驱动因素联系起来揭示了替代肿瘤进展路径中的趋同功能
DOI：
10.1038/s41598-019-39875-y
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发表时间：
2019
影响因子：
4.6
通讯作者：
Feltus, F. Alex
中科院分区：
文献类型：
--
作者：
Poehlman, William L.;Hsieh, James J.;Feltus, F. Alex
肾细胞癌(RCC)亚型具有不同的分子特征。利用1,009个肾癌样本的RNA表达谱，我们构建了一个条件注释的基因共表达网络(GCN)。RCC GCN包含针对包括RCC亚型和肿瘤分期在内的特定条件的二元基因共表达关系(EDGE)。作为该资源的应用，我们发现了与已知RCC驱动基因中的遗传损害相关的RCC GCN边缘和模块，包括VHL，一种常见的起始透明细胞RCC(CcRCC)遗传损害，以及PBRM1和BAP1，它们是辫状癌河模型(BCRM)中的早期遗传损害。由于具有PBRM1突变的ccRCC肿瘤与具有BAP1突变的肿瘤对靶向治疗的反应不同，我们专注于与呈现替代突变特征的肿瘤相关的ccRCC特定边缘：VHL-PBRM1或VHL-BAP1。我们发现了与这两条突变途径相关的特定混合分子功能。尽管这些突变相关的边缘具有独特的基因，但它们具有相同的免疫功能，这表明与BCRM一致的替代基因集具有收敛的功能作用。本文描述的RCC GCN是一种新的数据挖掘资源，用于分配具有特定分子和突变特征的多基因生物标记物及其与肾癌肿瘤的关系。
Renal cell carcinoma (RCC) subtypes are characterized by distinct molecular profiles. Using RNA expression profiles from 1,009 RCC samples, we constructed a condition-annotated gene coexpression network (GCN). The RCC GCN contains binary gene coexpression relationships (edges) specific to conditions including RCC subtype and tumor stage. As an application of this resource, we discovered RCC GCN edges and modules that were associated with genetic lesions in known RCC driver genes, including VHL, a common initiating clear cell RCC (ccRCC) genetic lesion, and PBRM1 and BAP1 which are early genetic lesions in the Braided Cancer River Model (BCRM). Since ccRCC tumors with PBRM1 mutations respond to targeted therapy differently than tumors with BAP1 mutations, we focused on ccRCC-specific edges associated with tumors that exhibit alternate mutation profiles: VHL-PBRM1 or VHL-BAP1. We found specific blends molecular functions associated with these two mutation paths. Despite these mutation-associated edges having unique genes, they were enriched for the same immunological functions suggesting a convergent functional role for alternate gene sets consistent with the BCRM. The condition annotated RCC GCN described herein is a novel data mining resource for the assignment of polygenic biomarkers and their relationships to RCC tumors with specific molecular and mutational profiles.
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影响因子：
11.2
作者：
Varn FS;Wang Y;Mullins DW;Fiering S;Cheng C
通讯作者：
Cheng C
影响因子：
30.8
作者：
Weinstein, John N.;Collisson, Eric A.;Mills, Gordon B.;Shaw, Kenna R. Mills;Ozenberger, Brad A.;Ellrott, Kyle;Shmulevich, Ilya;Sander, Chris;Stuart, Joshua M.
通讯作者：
Stuart, Joshua M.
影响因子：
4.6
作者：
Ficklin SP;Dunwoodie LJ;Poehlman WL;Watson C;Roche KE;Feltus FA
通讯作者：
Feltus FA
影响因子：
11.2
作者：
Tsai MC;Spitale RC;Chang HY
通讯作者：
Chang HY
TMPRSS3 是一种新的乳腺癌不良预后因素。
影响因子：
1.4
作者：
Xue Rui;Yanshu Li;F. Jin;Feng Li
通讯作者：
Feng Li