TY - JOUR
T1 - Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer
AU - TCGA Research Network
AU - Robertson, A. Gordon
AU - Kim, Jaegil
AU - Al-Ahmadie, Hikmat
AU - Bellmunt, Joaquim
AU - Guo, Guangwu
AU - Cherniack, Andrew D.
AU - Hinoue, Toshinori
AU - Laird, Peter W.
AU - Hoadley, Katherine A.
AU - Akbani, Rehan
AU - Castro, Mauro A.A.
AU - Gibb, Ewan A.
AU - Kanchi, Rupa S.
AU - Gordenin, Dmitry A.
AU - Shukla, Sachet A.
AU - Sanchez-Vega, Francisco
AU - Hansel, Donna E.
AU - Czerniak, Bogdan A.
AU - Reuter, Victor E.
AU - Su, Xiaoping
AU - Carvalho, Benilton de Sa
AU - Chagas, Vinicius S.
AU - Mungall, Karen L.
AU - Sadeghi, Sara
AU - Pedamallu, Chandra Sekhar
AU - Lu, Yiling
AU - Klimczak, Leszek J.
AU - Zhang, Jiexin
AU - Choo, Caleb
AU - Ojesina, Akinyemi I.
AU - Bullman, Susan
AU - Leraas, Kristen M.
AU - Lichtenberg, Tara M.
AU - Wu, Catherine J.
AU - Schultz, Nicholaus
AU - Getz, Gad
AU - Meyerson, Matthew
AU - Mills, Gordon B.
AU - McConkey, David J.
AU - Weinstein, John N.
AU - Kwiatkowski, David J.
AU - Lerner, Seth P.
AU - Albert, Monique
AU - Alexopoulou, Iakovina
AU - Ally, Adrian
AU - Antic, Tatjana
AU - Aron, Manju
AU - Balasundaram, Miruna
AU - Bartlett, John
AU - Singh, Parminder
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/10/19
Y1 - 2017/10/19
N2 - 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. A multiplatform analysis of 412 muscle-invasive bladder cancer patients provides insights into mutational profiles with prognostic value and establishes a framework associating distinct tumor subtypes with clinical options.
AB - 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. A multiplatform analysis of 412 muscle-invasive bladder cancer patients provides insights into mutational profiles with prognostic value and establishes a framework associating distinct tumor subtypes with clinical options.
KW - APOBEC mutation
KW - DNA methylation
KW - basal mRNA subtype
KW - lncRNA transcriptome
KW - luminal mRNA subtype
KW - microRNA
KW - muscle-invasive bladder cancer
KW - neoantigen
KW - neuronal subtype
KW - regulon
UR - https://www.scopus.com/pages/publications/85030652738
UR - https://www.scopus.com/pages/publications/85030652738#tab=citedBy
U2 - 10.1016/j.cell.2017.09.007
DO - 10.1016/j.cell.2017.09.007
M3 - Article
C2 - 28988769
AN - SCOPUS:85030652738
SN - 0092-8674
VL - 171
SP - 540-556.e25
JO - Cell
JF - Cell
IS - 3
ER -