Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.

Cell
Authors
Keywords
Abstract

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.

Year of Publication
2017
Journal
Cell
Volume
171
Issue
3
Pages
540-556.e25
Date Published
2017 Oct 19
ISSN
1097-4172
DOI
10.1016/j.cell.2017.09.007
PubMed ID
28988769
PubMed Central ID
PMC5687509
Links
Grant list
P50 CA091846 / CA / NCI NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
U24 CA143882 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
HHSN261201000032C / CA / NCI NIH HHS / United States
HHSN261201000021C / CP / NCI NIH HHS / United States
P50 CA100632 / CA / NCI NIH HHS / United States
U24 CA143866 / CA / NCI NIH HHS / United States
P30 CA016086 / CA / NCI NIH HHS / United States
U24 CA210950 / CA / NCI NIH HHS / United States
P01 CA120964 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
U01 CA168394 / CA / NCI NIH HHS / United States
U01 CA217842 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
R50 CA211482 / CA / NCI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
U24 CA210974 / CA / NCI NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
R01 CA155010 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
R01 CA178744 / CA / NCI NIH HHS / United States
U24 CA210949 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
U24 CA210999 / CA / NCI NIH HHS / United States
HHSN261200800001C / RC / CCR NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U24 CA199461 / CA / NCI NIH HHS / United States
U24 CA209851 / CA / NCI NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States
R50 CA221675 / CA / NCI NIH HHS / United States
K23 CA160664 / CA / NCI NIH HHS / United States
UL1 TR000371 / TR / NCATS NIH HHS / United States