Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

被引:438
作者
Robertson, A. Gordon [1 ]
Kim, Jaegil [2 ]
Al-Ahmadie, Hikmat [3 ]
Bellmunt, Joaquim [4 ,5 ]
Guo, Guangwu [5 ,6 ]
Cherniack, Andrew D. [2 ]
Hinoue, Toshinori [7 ]
Laird, Peter W. [7 ]
Hoadley, Katherine A. [8 ]
Akbani, Rehan [9 ]
Castro, Mauro A. A. [10 ]
Gibb, Ewan A. [1 ]
Kanchi, Rupa S. [9 ]
Gordenin, Dmitry A. [11 ]
Shukla, Sachet A. [5 ,6 ]
Sanchez-Vega, Francisco [12 ]
Hansel, Donna E. [13 ]
Czerniak, Bogdan A. [14 ]
Reuter, Victor E. [3 ]
Su, Xiaoping [9 ]
Carvalho, Benilton de Sa [15 ]
Chagas, Vinicius S. [10 ]
Mungall, Karen L. [1 ]
Sadeghi, Sara [1 ]
Pedamallu, Chandra Sekhar [2 ]
Lu, Yiling [16 ]
Klimczak, Leszek J. [17 ]
Zhang, Jiexin [9 ]
Choo, Caleb [1 ]
Ojesina, Akinyemi I. [18 ]
Bullman, Susan [2 ]
Leraas, Kristen M. [19 ]
Lichtenberg, Tara M. [19 ]
Wu, Catherine J. [20 ]
Schultz, Nicholaus [12 ]
Getz, Gad [2 ]
Meyerson, Matthew [5 ,21 ]
Mills, Gordon B. [16 ]
McConkey, David J. [22 ]
Weinstein, John N. [9 ,16 ]
Kwiatkowski, David J. [23 ]
Lerner, Seth P. [24 ]
机构
[1] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada
[2] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA
[3] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA
[4] Dana Farber Canc Inst, Bladder Canc Ctr, Dept Med, PSMAR IMIM Lab, Boston, MA 02215 USA
[5] Harvard Univ, Boston, MA 02115 USA
[6] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[7] Van Andel Res Inst, Ctr Epigenet, Grand Rapids, MI 49503 USA
[8] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27514 USA
[9] Univ Texas Houston, MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, 1515 Holcombe Blvd, Houston, TX 77030 USA
[10] Univ Fed Parana, Polytech Ctr, Bioinformat & Syst Biol Lab, BR-80060000 Curitiba, Parana, Brazil
[11] NIEHS, NIH, Genome Integr & Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA
[12] Mem Sloan Kettering Canc Ctr, Ctr Mol Oncol, New York, NY 10065 USA
[13] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA
[14] Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, 1515 Holcombe Blvd, Houston, TX 77030 USA
[15] Univ Estadual Campinas, Dept Stat, Biostat & Computat Biol Lab, BR-13083859 Sao Paulo, Brazil
[16] Univ Texas Houston, MD Anderson Canc Ctr, Dept Syst Biol, 1515 Holcombe Blvd, Houston, TX 77030 USA
[17] NIEHS, NIH, Integrat Bioinformat Support Grp, POB 12233, Res Triangle Pk, NC 27709 USA
[18] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA
[19] Res Inst Nationwide Childrens Hosp, Biospecimen Core Resource, Columbus, OH 43205 USA
[20] Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA
[21] Dana Farber Canc Inst, Pathol & Med Oncol, Boston, MA 02115 USA
[22] Johns Hopkins Univ, Greenberg Bladder Canc Inst, Baltimore, MD 21218 USA
[23] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[24] Baylor Coll Med, Dan L Duncan Canc Ctr, Scott Dept Urol, Houston, TX 77030 USA
关键词
SOMATIC ERCC2 MUTATIONS; PHASE PROTEIN ARRAY; UROTHELIAL CARCINOMA; GENETIC ALTERATIONS; LUMINAL SUBTYPES; EXPRESSION; RECEPTOR; ACCURATE; BASAL; QUANTIFICATION;
D O I
10.1016/j.cell.2017.09.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We report a comprehensive analysis of 412 muscleinvasive 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.
引用
收藏
页码:540 / +
页数:42
相关论文
共 114 条
[1]   Biological determinants of bladder cancer gene expression subtypes [J].
Aine, Mattias ;
Eriksson, Pontus ;
Liedberg, Fredrik ;
Sjodahl, Gottfrid ;
Hoglund, Mattias .
SCIENTIFIC REPORTS, 2015, 5
[2]   A pan-cancer proteomic perspective on The Cancer Genome Atlas [J].
Akbani, Rehan ;
Ng, Patrick Kwok Shing ;
Werner, Henrica M. J. ;
Shahmoradgoli, Maria ;
Zhang, Fan ;
Ju, Zhenlin ;
Liu, Wenbin ;
Yang, Ji-Yeon ;
Yoshihara, Kosuke ;
Li, Jun ;
Ling, Shiyun ;
Seviour, Elena G. ;
Ram, Prahlad T. ;
Minna, John D. ;
Diao, Lixia ;
Tong, Pan ;
Heymach, John V. ;
Hill, Steven M. ;
Dondelinger, Frank ;
Stadler, Nicolas ;
Byers, Lauren A. ;
Meric-Bernstam, Funda ;
Weinstein, John N. ;
Broom, Bradley M. ;
Verhaak, Roeland G. W. ;
Liang, Han ;
Mukherjee, Sach ;
Lu, Yiling ;
Mills, Gordon B. .
NATURE COMMUNICATIONS, 2014, 5
[3]   Frequent somatic CDH1 loss-of-function mutations in plasmacytoid variant bladder cancer [J].
Al-Ahmadie, Hikmat A. ;
Iyer, Gopa ;
Lee, Byron H. ;
Scott, Sasinya N. ;
Mehra, Rohit ;
Bagrodia, Aditya ;
Jordan, Emmet J. ;
Gao, Sizhi Paul ;
Ramirez, Ricardo ;
Cha, Eugene K. ;
Desai, Neil B. ;
Zabor, Emily C. ;
Ostrovnaya, Irina ;
Gopalan, Anuradha ;
Chen, Ying-Bei ;
Fine, Samson W. ;
Tickoo, Satish K. ;
Gandhi, Anupama ;
Hreiki, Joseph ;
Viale, Agnss ;
Arcila, Maria E. ;
Dalbagni, Guido ;
Rosenberg, Jonathan E. ;
Bochner, Bernard H. ;
Bajorin, Dean F. ;
Berger, Michael F. ;
Reuter, Victor E. ;
Taylor, Barry S. ;
Solit, David B. .
NATURE GENETICS, 2016, 48 (04) :356-+
[4]   Signatures of mutational processes in human cancer [J].
Alexandrov, Ludmil B. ;
Nik-Zainal, Serena ;
Wedge, David C. ;
Aparicio, Samuel A. J. R. ;
Behjati, Sam ;
Biankin, Andrew V. ;
Bignell, Graham R. ;
Bolli, Niccolo ;
Borg, Ake ;
Borresen-Dale, Anne-Lise ;
Boyault, Sandrine ;
Burkhardt, Birgit ;
Butler, Adam P. ;
Caldas, Carlos ;
Davies, Helen R. ;
Desmedt, Christine ;
Eils, Roland ;
Eyfjord, Jorunn Erla ;
Foekens, John A. ;
Greaves, Mel ;
Hosoda, Fumie ;
Hutter, Barbara ;
Ilicic, Tomislav ;
Imbeaud, Sandrine ;
Imielinsk, Marcin ;
Jaeger, Natalie ;
Jones, David T. W. ;
Jones, David ;
Knappskog, Stian ;
Kool, Marcel ;
Lakhani, Sunil R. ;
Lopez-Otin, Carlos ;
Martin, Sancha ;
Munshi, Nikhil C. ;
Nakamura, Hiromi ;
Northcott, Paul A. ;
Pajic, Marina ;
Papaemmanuil, Elli ;
Paradiso, Angelo ;
Pearson, John V. ;
Puente, Xose S. ;
Raine, Keiran ;
Ramakrishna, Manasa ;
Richardson, Andrea L. ;
Richter, Julia ;
Rosenstiel, Philip ;
Schlesner, Matthias ;
Schumacher, Ton N. ;
Span, Paul N. ;
Teague, Jon W. .
NATURE, 2013, 500 (7463) :415-+
[5]   Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].
Altschul, SF ;
Madden, TL ;
Schaffer, AA ;
Zhang, JH ;
Zhang, Z ;
Miller, W ;
Lipman, DJ .
NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402
[6]   Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy [J].
Balbas-Martinez, Cristina ;
Sagrera, Ana ;
Carrillo-de-Santa-Pau, Enrique ;
Earl, Julie ;
Marquez, Mirari ;
Vazquez, Miguel ;
Lapi, Eleonora ;
Castro-Giner, Francesc ;
Beltran, Sergi ;
Bayes, Monica ;
Carrato, Alfredo ;
Cigudosa, Juan C. ;
Dominguez, Orlando ;
Gut, Marta ;
Herranz, Jesus ;
Juanpere, Nuria ;
Kogevinas, Manolis ;
Langa, Xavier ;
Lopez-Knowles, Elena ;
Lorente, Jose A. ;
Lloreta, Josep ;
Pisano, David G. ;
Richart, Laia ;
Rico, Daniel ;
Salgado, Rocio N. ;
Tardon, Adonina ;
Chanock, Stephen ;
Heath, Simon ;
Valencia, Alfonso ;
Losada, Ana ;
Gut, Ivo ;
Malats, Nuria ;
Real, Francisco X. .
NATURE GENETICS, 2013, 45 (12) :1464-U221
[7]   High density DNA methylation array with single CpG site resolution [J].
Bibikova, Marina ;
Barnes, Bret ;
Tsan, Chan ;
Ho, Vincent ;
Klotzle, Brandy ;
Le, Jennie M. ;
Delano, David ;
Zhang, Lu ;
Schroth, Gary P. ;
Gunderson, Kevin L. ;
Fan, Jian-Bing ;
Shen, Richard .
GENOMICS, 2011, 98 (04) :288-295
[8]   Genome-wide DNA methylation profiling using Infinium® assay [J].
Bibikova, Marina ;
Le, Jennie ;
Barnes, Bret ;
Saedinia-Melnyk, Shadi ;
Zhou, Lixin ;
Shen, Richard ;
Gunderson, Kevin L. .
EPIGENOMICS, 2009, 1 (01) :177-200
[9]   Independent Component Analysis Uncovers the Landscape of the Bladder Tumor Transcriptome and Reveals Insights into Luminal and Basal Subtypes [J].
Biton, Anne ;
Bernard-Pierrot, Isabelle ;
Lou, Yinjun ;
Krucker, Clementine ;
Chapeaublanc, Elodie ;
Rubio-Perez, Carlota ;
Lopez-Bigas, Nuria ;
Kamoun, Aurelie ;
Neuzillet, Yann ;
Gestraud, Pierre ;
Grieco, Luca ;
Rebouissou, Sandra ;
de Reynies, Aurelien ;
Benhamou, Simone ;
Lebret, Thierry ;
Southgate, Jennifer ;
Barillot, Emmanuel ;
Allory, Yves ;
Zinovyev, Andrei ;
Radvanyi, Francois .
CELL REPORTS, 2014, 9 (04) :1235-1245
[10]   ESR1, ERBB2, and Ki67 mRNA expression predicts stage and grade of non-muscle-invasive bladder carcinoma (NMIBC) [J].
Breyer, Johannes ;
Wirtz, Ralph M. ;
Laible, Mark ;
Schlombs, Kornelia ;
Erben, Philipp ;
Kriegmair, Maximilian Christian ;
Stoehr, Robert ;
Eidt, Sebastian ;
Denzinger, Stefan ;
Burger, Maximilian ;
Hartmann, Arndt ;
Otto, Wolfgang .
VIRCHOWS ARCHIV, 2016, 469 (05) :547-552