肌层浸润性膀胱癌的综合分子特征分析
Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.
作者信息
Robertson A Gordon, Kim Jaegil, Al-Ahmadie Hikmat, Bellmunt Joaquim, Guo Guangwu, Cherniack Andrew D, Hinoue Toshinori, Laird Peter W, Hoadley Katherine A, Akbani Rehan, Castro Mauro A A, Gibb Ewan A, Kanchi Rupa S, Gordenin Dmitry A, Shukla Sachet A, Sanchez-Vega Francisco, Hansel Donna E, Czerniak Bogdan A, Reuter Victor E, Su Xiaoping, de Sa Carvalho Benilton, Chagas Vinicius S, Mungall Karen L, Sadeghi Sara, Pedamallu Chandra Sekhar, Lu Yiling, Klimczak Leszek J, Zhang Jiexin, Choo Caleb, Ojesina Akinyemi I, Bullman Susan, Leraas Kristen M, Lichtenberg Tara M, Wu Catherine J, Schultz Nicholaus, Getz Gad, Meyerson Matthew, Mills Gordon B, McConkey David J, Weinstein John N, Kwiatkowski David J, Lerner Seth P
机构信息
Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
Cancer Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
出版信息
Cell. 2017 Oct 19;171(3):540-556.e25. doi: 10.1016/j.cell.2017.09.007. Epub 2017 Oct 5.
We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.
我们报告了一项对412例肌肉浸润性膀胱癌的综合分析，该分析采用了多个TCGA分析平台。58个基因发生了显著突变，总体突变负荷与APOBEC特征性诱变有关。通过突变特征进行聚类，确定了一个5年生存率为75%的高突变亚组。mRNA表达聚类完善了先前的聚类分析，并确定了一个预后不良的“神经元”亚型，其中大多数肿瘤缺乏小细胞或神经内分泌组织学特征。通过mRNA、长链非编码RNA（lncRNA）和miRNA表达进行聚类，最终确定了具有不同上皮-间质转化状态、原位癌评分、组织学特征和生存率的亚组。我们的分析确定了5种表达亚型，这些亚型可能对不同治疗的反应进行分层。
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