. 2017 Oct 19;171(3):540-556.e25.

doi: 10.1016/j.cell.2017.09.007. Epub 2017 Oct 5.

Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

A Gordon Robertson¹, Jaegil Kim², Hikmat Al-Ahmadie³, Joaquim Bellmunt⁴, Guangwu Guo⁵, Andrew D Cherniack², Toshinori Hinoue⁶, Peter W Laird⁶, Katherine A Hoadley⁷, Rehan Akbani⁸, Mauro A A Castro⁹, Ewan A Gibb¹, Rupa S Kanchi⁸, Dmitry A Gordenin¹⁰, Sachet A Shukla⁵, Francisco Sanchez-Vega¹¹, Donna E Hansel¹², Bogdan A Czerniak¹³, Victor E Reuter³, Xiaoping Su⁸, Benilton de Sa Carvalho¹⁴, Vinicius S Chagas⁹, Karen L Mungall¹, Sara Sadeghi¹, Chandra Sekhar Pedamallu², Yiling Lu¹⁵, Leszek J Klimczak¹⁶, Jiexin Zhang⁸, Caleb Choo¹, Akinyemi I Ojesina¹⁷, Susan Bullman², Kristen M Leraas¹⁸, Tara M Lichtenberg¹⁸, Catherine J Wu¹⁹, Nicholaus Schultz¹¹, Gad Getz², Matthew Meyerson²⁰, Gordon B Mills¹⁵, David J McConkey²¹; TCGA Research Network; John N Weinstein²², David J Kwiatkowski²³, Seth P Lerner²⁴

Collaborators, Affiliations

Collaborators

TCGA Research Network:
Rehan Akbani, Hikmat Al-Ahmadie, Monique Albert, Iakovina Alexopoulou, Adrian Ally, Tatjana Antic, Manju Aron, Miruna Balasundaram, John Bartlett, Stephen B Baylin, Allison Beaver, Joaquim Bellmunt, Inanc Birol, Lori Boice, Moiz S Bootwalla, Jay Bowen, Reanne Bowlby, Denise Brooks, Bradley M Broom, Wiam Bshara, Susan Bullman, Eric Burks, Flavio M Cárcano, Rebecca Carlsen, Benilton S Carvalho, Andre L Carvalho, Eric P Castle, Mauro A A Castro, Patricia Castro, James W Catto, Vinicius S Chagas, Andrew D Cherniack, David W Chesla, Caleb Choo, Eric Chuah, Sudha Chudamani, Victoria K Cortessis, Sandra L Cottingham, Daniel Crain, Erin Curley, Bogdan A Czerniak, Siamak Daneshmand, John A Demchok, Noreen Dhalla, Hooman Djaladat, John Eckman, Sophie C Egea, Jay Engel, Ina Felau, Martin L Ferguson, Johanna Gardner, Julie M Gastier-Foster, Mark Gerken, Gad Getz, Ewan A Gibb, Carmen R Gomez-Fernandez, Dmitry A Gordenin, Guangwu Guo, Donna E Hansel, Jodi Harr, Arndt Hartmann, Lynn M Herbert, Toshinori Hinoue, Thai H Ho, Katherine A Hoadley, Robert A Holt, Carolyn M Hutter, Steven J M Jones, Merce Jorda, Richard J Kahnoski, Rupa S Kanchi, Katayoon Kasaian, Jaegil Kim, Leszek J Klimczak, David J Kwiatkowski, Phillip H Lai, Peter W Laird, Brian R Lane, Kristen M Leraas, Seth P Lerner, Tara M Lichtenberg, Jia Liu, Laxmi Lolla, Yair Lotan, Yiling Lu, Fabiano R Lucchesi, Yussanne Ma, Roberto D Machado, Dennis T Maglinte, David Mallery, Marco A Marra, Sue E Martin, Michael Mayo, David J McConkey, Anoop Meraney, Matthew Meyerson, Gordon B Mills, Alireza Moinzadeh, Richard A Moore, Edna M Mora Pinero, Scott Morris, Carl Morrison, Karen L Mungall, Andrew J Mungall, Jerome B Myers, Rashi Naresh, Peter H O'Donnell, Akinyemi I Ojesina, Dipen J Parekh, Jeremy Parfitt, Joseph D Paulauskis, Chandra Sekhar Pedamallu, Robert J Penny, Todd Pihl, Sima Porten, Mario E Quintero-Aguilo, Nilsa C Ramirez, W Kimryn Rathmell, Victor E Reuter, Kimberly Rieger-Christ, A Gordon Robertson, Sara Sadeghi, Charles Saller, Andrew Salner, Francisco Sanchez-Vega, George Sandusky, Cristovam Scapulatempo-Neto, Jacqueline E Schein, Anne K Schuckman, Nikolaus Schultz, Candace Shelton, Troy Shelton, Sachet A Shukla, Jeff Simko, Parminder Singh, Payal Sipahimalani, Norm D Smith, Heidi J Sofia, Andrea Sorcini, Melissa L Stanton, Gary D Steinberg, Robert Stoehr, Xiaoping Su, Travis Sullivan, Qiang Sun, Angela Tam, Roy Tarnuzzer, Katherine Tarvin, Helge Taubert, Nina Thiessen, Leigh Thorne, Kane Tse, Kelinda Tucker, David J Van Den Berg, Kim E van Kessel, Sven Wach, Yunhu Wan, Zhining Wang, John N Weinstein, Daniel J Weisenberger, Lisa Wise, Tina Wong, Ye Wu, Catherine J Wu, Liming Yang, Leigh Anne Zach, Jean C Zenklusen, Jiashan Julia Zhang, Jiexin Zhang, Erik Zmuda, Ellen C Zwarthoff

Affiliations

¹ Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
² Cancer Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
³ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁴ PSMAR-IMIM Lab, Bladder Cancer Center, Department of Medicine, Dana-Farber Cancer Institute and Harvard University, Boston, MA 02215, USA.
⁵ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard University, Boston, MA 02115, USA.
⁶ Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
⁷ Department of Genetics, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
⁸ Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁹ Bioinformatics and Systems Biology Laboratory, Federal University of Paraná Polytechnic Center, Curitiba, PR CEP 80.060-000, Brazil.
¹⁰ Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
¹¹ Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
¹² Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
¹³ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁴ Biostatistics and Computational Biology Laboratory, Department of Statistics, University of Campinas, São Paulo, 13.083-859, Brazil.
¹⁵ Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁶ Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
¹⁷ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
¹⁸ Biospecimen Core Resource, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
¹⁹ Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
²⁰ Pathology and Medical Oncology, Dana-Farber Cancer Institute and Harvard University, Boston, MA 02115, USA.
²¹ Greenberg Bladder Cancer Institute, Johns Hopkins University, Baltimore, MD 21218, USA.
²² Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA. Electronic address: jweinste@mdanderson.org.
²³ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: dk@rics.bwh.harvard.edu.
²⁴ Scott Department of Urology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: slerner@bcm.edu.

PMID: 28988769
PMCID: PMC5687509
DOI: 10.1016/j.cell.2017.09.007

Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

A Gordon Robertson et al. Cell. 2017.

. 2017 Oct 19;171(3):540-556.e25.

doi: 10.1016/j.cell.2017.09.007. Epub 2017 Oct 5.

Authors

Collaborators

TCGA Research Network:
Rehan Akbani, Hikmat Al-Ahmadie, Monique Albert, Iakovina Alexopoulou, Adrian Ally, Tatjana Antic, Manju Aron, Miruna Balasundaram, John Bartlett, Stephen B Baylin, Allison Beaver, Joaquim Bellmunt, Inanc Birol, Lori Boice, Moiz S Bootwalla, Jay Bowen, Reanne Bowlby, Denise Brooks, Bradley M Broom, Wiam Bshara, Susan Bullman, Eric Burks, Flavio M Cárcano, Rebecca Carlsen, Benilton S Carvalho, Andre L Carvalho, Eric P Castle, Mauro A A Castro, Patricia Castro, James W Catto, Vinicius S Chagas, Andrew D Cherniack, David W Chesla, Caleb Choo, Eric Chuah, Sudha Chudamani, Victoria K Cortessis, Sandra L Cottingham, Daniel Crain, Erin Curley, Bogdan A Czerniak, Siamak Daneshmand, John A Demchok, Noreen Dhalla, Hooman Djaladat, John Eckman, Sophie C Egea, Jay Engel, Ina Felau, Martin L Ferguson, Johanna Gardner, Julie M Gastier-Foster, Mark Gerken, Gad Getz, Ewan A Gibb, Carmen R Gomez-Fernandez, Dmitry A Gordenin, Guangwu Guo, Donna E Hansel, Jodi Harr, Arndt Hartmann, Lynn M Herbert, Toshinori Hinoue, Thai H Ho, Katherine A Hoadley, Robert A Holt, Carolyn M Hutter, Steven J M Jones, Merce Jorda, Richard J Kahnoski, Rupa S Kanchi, Katayoon Kasaian, Jaegil Kim, Leszek J Klimczak, David J Kwiatkowski, Phillip H Lai, Peter W Laird, Brian R Lane, Kristen M Leraas, Seth P Lerner, Tara M Lichtenberg, Jia Liu, Laxmi Lolla, Yair Lotan, Yiling Lu, Fabiano R Lucchesi, Yussanne Ma, Roberto D Machado, Dennis T Maglinte, David Mallery, Marco A Marra, Sue E Martin, Michael Mayo, David J McConkey, Anoop Meraney, Matthew Meyerson, Gordon B Mills, Alireza Moinzadeh, Richard A Moore, Edna M Mora Pinero, Scott Morris, Carl Morrison, Karen L Mungall, Andrew J Mungall, Jerome B Myers, Rashi Naresh, Peter H O'Donnell, Akinyemi I Ojesina, Dipen J Parekh, Jeremy Parfitt, Joseph D Paulauskis, Chandra Sekhar Pedamallu, Robert J Penny, Todd Pihl, Sima Porten, Mario E Quintero-Aguilo, Nilsa C Ramirez, W Kimryn Rathmell, Victor E Reuter, Kimberly Rieger-Christ, A Gordon Robertson, Sara Sadeghi, Charles Saller, Andrew Salner, Francisco Sanchez-Vega, George Sandusky, Cristovam Scapulatempo-Neto, Jacqueline E Schein, Anne K Schuckman, Nikolaus Schultz, Candace Shelton, Troy Shelton, Sachet A Shukla, Jeff Simko, Parminder Singh, Payal Sipahimalani, Norm D Smith, Heidi J Sofia, Andrea Sorcini, Melissa L Stanton, Gary D Steinberg, Robert Stoehr, Xiaoping Su, Travis Sullivan, Qiang Sun, Angela Tam, Roy Tarnuzzer, Katherine Tarvin, Helge Taubert, Nina Thiessen, Leigh Thorne, Kane Tse, Kelinda Tucker, David J Van Den Berg, Kim E van Kessel, Sven Wach, Yunhu Wan, Zhining Wang, John N Weinstein, Daniel J Weisenberger, Lisa Wise, Tina Wong, Ye Wu, Catherine J Wu, Liming Yang, Leigh Anne Zach, Jean C Zenklusen, Jiashan Julia Zhang, Jiexin Zhang, Erik Zmuda, Ellen C Zwarthoff

Affiliations

¹ Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
² Cancer Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
³ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁴ PSMAR-IMIM Lab, Bladder Cancer Center, Department of Medicine, Dana-Farber Cancer Institute and Harvard University, Boston, MA 02215, USA.
⁵ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard University, Boston, MA 02115, USA.
⁶ Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
⁷ Department of Genetics, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
⁸ Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁹ Bioinformatics and Systems Biology Laboratory, Federal University of Paraná Polytechnic Center, Curitiba, PR CEP 80.060-000, Brazil.
¹⁰ Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
¹¹ Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
¹² Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
¹³ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁴ Biostatistics and Computational Biology Laboratory, Department of Statistics, University of Campinas, São Paulo, 13.083-859, Brazil.
¹⁵ Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁶ Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
¹⁷ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
¹⁸ Biospecimen Core Resource, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
¹⁹ Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
²⁰ Pathology and Medical Oncology, Dana-Farber Cancer Institute and Harvard University, Boston, MA 02115, USA.
²¹ Greenberg Bladder Cancer Institute, Johns Hopkins University, Baltimore, MD 21218, USA.
²² Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA. Electronic address: jweinste@mdanderson.org.
²³ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: dk@rics.bwh.harvard.edu.
²⁴ Scott Department of Urology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: slerner@bcm.edu.

PMID: 28988769
PMCID: PMC5687509
DOI: 10.1016/j.cell.2017.09.007

Erratum in

Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.
Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD, Hinoue T, Laird PW, Hoadley KA, Akbani R, Castro MAA, Gibb EA, Kanchi RS, Gordenin DA, Shukla SA, Sanchez-Vega F, Hansel DE, Czerniak BA, Reuter VE, Su X, de Sa Carvalho B, Chagas VS, Mungall KL, Sadeghi S, Pedamallu CS, Lu Y, Klimczak LJ, Zhang J, Choo C, Ojesina AI, Bullman S, Leraas KM, Lichtenberg TM, Wu CJ, Schultz N, Getz G, Meyerson M, Mills GB, McConkey DJ; TCGA Research Network; Weinstein JN, Kwiatkowski DJ, Lerner SP. Robertson AG, et al. Cell. 2018 Aug 9;174(4):1033. doi: 10.1016/j.cell.2018.07.036. Cell. 2018. PMID: 30096301 Free PMC article. No abstract available.

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.

Keywords: APOBEC mutation; DNA methylation; basal mRNA subtype; lncRNA transcriptome; luminal mRNA subtype; microRNA; muscle-invasive bladder cancer; neoantigen; neuronal subtype; regulon.

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Conflict of interest statement

Potential conflicts of interest

S.P.L. has received investigator initiated research funding from Endo Pharmaceuticals; support for a clinical trial from FKD and Viventia; is a consultant for UroGen, Vaxiion, Nucleix and BioCancell. A.D.C., G.G. and M.M have received research funding from Bayer AG. E.A.G. is now employed by GenomeDx Biosciences. M.M. has no current conflicts; was previously an equity holder in and consultant for Foundation Medicine. G.B.M. is a member of the scientific advisory board and receives research support from AstraZeneca. D.J.M. has stock options in ApoCell, Inc. J.B. has a paid consultancy with Pfizer; has received advisory board and lecture fees from Merck; has received advisory board fees from Genentech; has given uncompensated presentations at Genentech. C.J.W. is a cofounder and advisory board member of Neon Therapeutics. No other conflicts of interest declared.

Figures

**Figure 1. Landscape of mutational signatures, mutations and copy number alterations**
(A) Alteration landscape for 412 primary tumours. Top to bottom: Synonymous and non-synonymous somatic mutation rates, with one ultra-mutated sample with a POLE signature. Mutational signature (MSig) cluster, APOBEC mutation load, and neoantigen load by quartile. Normalized activity of 4 mutational signatures. Combined tumor stage (T1,2 vs. T3,4) and node status, papillary histology, and gender. Somatic mutations for significantly mutated genes (SMGs) with frequency ≥ 7%. Copy number alterations for selected genes, and FGFR3 and PPARG gene fusions. (B) Kaplan-Meier plots for overall survival (L to R): Overall mutation burden (SNVs); Mutation signature clusters (MSig1–4); APOBEC-mediated mutation load; Neoantigen load;

**Figure 2. mRNA expression subtypes**
Top, L to R: 5 mRNA expression subtypes: luminal-papillary, luminal-infiltrated, luminal, basal-squamous and neuronal. Covariates: 4 previously reported TCGA subtypes; selected clinical covariates and key genetic alterations; normalized expression for miRNAs and proteins; log₂ (fold change against the median expression across samples) for selected genes, for labeled gene sets. Samples within the three luminal subtypes, the basal-squamous subtype, and the neuronal subtype are ordered by luminal, basal, and neuroendocrine signature scores, respectively. Genes that are down-regulated* vs. up-regulated** in CIS.

**Figure 3. Somatic alterations in signaling pathways across mRNA subtypes**
Somatic alterations include mutations and copy-number changes (i.e. deep deletions and high-level amplifications, from GISTIC results). Missense mutations are counted only if they have known oncogenic function based on OncoKB (http://oncokb.org) annotations, or have previously been reported in COSMIC, or occur at known mutational hotspots. The table shows the fraction of samples with alterations in selected signaling pathways. In the pathway diagrams, edges show pairwise molecular interactions; boxes outlined in red denote alterations leading to pathway activation, while boxes outlined in blue denote predicted pathway inactivation. The oncoprint illustrates type and frequency of alteration, as well as patterns of co-occurrence, for selected genes from the pathways highlighted in the table.

**Figure 4. LncRNA expression subtypes**
(A) Heatmap and covariates for four unsupervised lncRNA consensus clusters. Top to bottom: normalized abundance heatmap for 171 lncRNAs; profile of silhouette width calculated from the consensus membership heatmap, W_cm; covariates for clinical parameters, molecular subtypes, purity, mutations in *TP53* and *FGFR3*, FGFR3 and PPARG gene fusions; row-scaled mRNA levels for 3 genes; collapsed CIS gene sets (Dyrskjot et al., 2004) (Methods; CIS up = genes up-regulated in CIS; CIS down = genes down-regulated in CIS); row-scaled regulon activity profiles (showing activated, undefined, or repressed status) for 23 regulators; RNA-seq-based EMT scores (Mak et al., 2016). The following p values are Bonferroni-corrected: for mutated genes (for 58 SMGs), gene fusions (for 23 fusions), regulon activity (for 23 regulators), and mRNA-seq (for 12 genes). (B) A Kaplan-Meier plot for overall 5-year survival according to lncRNA subtype.

**Figure 5. MicroRNA expression subtypes**
(A) Heatmap and covariates for a 4-cluster unsupervised consensus clustering solution. Top to bottom: Normalized heatmap showing a subset of 142 miRNAs that had a mean RPM ≥ 50 and an absolute value of tumour-vs-normal fold change ≥ 1.5. Profile of silhouette width calculated from the consensus membership heatmap, W_cm, with lower values indicating samples that are atypical cluster members. Covariate tracks for clinical parameters, genomic platform subtypes, purity, mutations in *TP53* and *FGFR3*, and FGFR3 and PPARG gene fusions. Row-scaled regulon activity profiles for 23 regulators that have been associated with bladder cancer. Row-scaled mRNA levels for 12 genes, then for collapsed CIS gene sets (Dyrskjot et al., 2004) (Methods; CIS up = genes up-regulated in CIS; CIS down = genes down-regulated in CIS); and RNA-seq-based EMT scores (Mak et al., 2016). The following p values are Bonferroni-corrected: for mutated genes (for 58 SMGs), gene fusions (for 23 fusions), regulon activity (for 23 regulators), and mRNA-seq (12 genes). (B) A Kaplan-Meier plot for overall survival data that has been censored at 5 years.

**Figure 6. Integrated analysis**
(A) Cluster of cluster assignments analysis (COCA). Unsupervised clustering of subtype calls. Subtype calls for mRNA (red), lncRNA (black), and miRNA (blue) are colored by separate data type. Annotations at the right of and below the heatmap use colors for mRNA subtypes. (B,C) Multivariate Cox analysis for overall survival. (B) Coefficients (β) from the LASSO-penalized multivariate Cox regression on 15 covariates that were significant (corrected p < 0.05) in univariate survival calculations. Dashed blue lines indicate |β| = 0.1; variables shown in grey text have coefficients with |β| < 0.1. (C) Kaplan-Meier plot predicted from the cohort, for three tertile risk groups, at 48 months.

**Figure 7**
Proposed schema of expression-based, subtype-stratified therapeutic approach as a framework for prospective hypothesis testing in clinical trials. * For luminal-papillary cases, the low predicted likelihood of response is based on preliminary data from (Seiler et al., 2017). See Discussion.

See this image and copyright information in PMC

Comment in

Re: Comprehensive Molecular Characterization of Muscle-invasive Bladder Cancer.
Saito R, Kobayashi T, Ogawa O. Saito R, et al. Eur Urol. 2018 May;73(5):808-809. doi: 10.1016/j.eururo.2017.12.010. Epub 2017 Dec 20. Eur Urol. 2018. PMID: 29274865 No abstract available.

References

1. Aine M, Eriksson P, Liedberg F, Sjodahl G, Hoglund M. Biological determinants of bladder cancer gene expression subtypes. Sci Rep. 2015;5:10957. - PMC - PubMed
1. Akbani R, Ng PK, Werner HM, Shahmoradgoli M, Zhang F, Ju Z, Liu W, Yang JY, Yoshihara K, Li J, et al. A pan-cancer proteomic perspective on The Cancer Genome Atlas. Nat Commun. 2014;5:3887. - PMC - PubMed
1. Al-Ahmadie HA, Iyer G, Lee BH, Scott SN, Mehra R, Bagrodia A, Jordan EJ, Gao SP, Ramirez R, Cha EK, et al. Frequent somatic CDH1 loss-of-function mutations in plasmacytoid variant bladder cancer. Nat Genet. 2016;48:356–358. - PMC - PubMed
1. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415–421. - PMC - PubMed
1. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997;25:3389–3402. - PMC - PubMed

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Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

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Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

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