Format

Send to

Choose Destination
See comment in PubMed Commons below
Nature. 2014 Mar 20;507(7492):315-22. doi: 10.1038/nature12965. Epub 2014 Jan 29.

Comprehensive molecular characterization of urothelial bladder carcinoma.

Collaborators (367)

Weinstein JN, Akbani R, Broom BM, Wang W, Verhaak RG, McConkey D, Lerner S, Morgan M, Creighton CJ, Smith C, Kwiatkowski DJ, Cherniack AD, Kim J, Sekhar Pedamallu C, Noble MS, Al-Ahmadie HA, Reuter VE, Rosenberg JE, Bajorin DF, Bochner BH, Solit DB, Koppie T, Robinson B, Gordenin DA, Fargo D, Klimczak LJ, Roberts SA, Au J, Laird PW, Hinoue T, Schultz N, Ramirez R, Hansel D, Hoadley KA, Kim WY, Damrauer JS, Baylin SB, Mungall AJ, Robertson AG, Chu A, Kwiatkowski DJ, Sougnez C, Cibulskis K, Lichtenstein L, Sivachenko A, Stewart C, Lawrence MS, Getz G, Lander E, Gabriel SB, Creighton CJ, Donehower L, Cherniack AD, Kim J, Carter SL, Saksena G, Schumacher SE, Sougnez C, Freeman SS, Jung J, Sekhar Pedamallu C, Bhatt AS, Pugh T, Getz G, Beroukhim R, Gabriel SB, Meyerson M, Mungall AJ, Robertson AG, Chu A, Ally A, Balasundaram M, Butterfield YS, Dhalla N, Hirst C, Holt RA, Jones SJ, Lee D, Li HI, Marra MA, Mayo M, Moore RA, Schein JE, Sipahimalani P, Tam A, Thiessen N, Wong T, Wye N, Bowlby R, Chuah E, Guin R, Jones SJ, Marra MA, Hinoue T, Shen H, Bootwalla MS, Triche T Jr, Lai PH, Van Den Berg DJ, Weisenberger DJ, Laird PW, Hansel D, Hoadley KA, Balu S, Bodenheimer T, Damrauer JS, Hoyle AP, Jefferys SR, Meng S, Mose LE, Simons JV, Soloway MG, Wu J, Kim WY, Parker JS, Hayes DN, Roach J, Buda E, Jones CD, Mieczkowski PA, Tan D, Veluvolu U, Waring S, Auman JT, Perou CM, Wilkerson MD, Santoso N, Parfenov M, Ren X, Pantazi A, Hadjipanayis A, Seidman J, Kucherlapati R, Lee S, Yang L, Park PJ, Baylin SB, Wei Xu A, Protopopov A, Zhang J, Bristow C, Mahadeshwar HS, Seth S, Song X, Tang J, Zeng D, Chin L, Guo C, Weinstein JN, Akbani R, Broom BM, McConkey D, Casasent TD, Liu W, Ju Z, Motter T, Peng B, Ryan M, Wang W, Verhaak RG, Su X, Yang JY, Lorenzi PL, Yao H, Zhang N, Zhang J, Mills GB, Kim J, Noble MS, Cho J, DiCara D, Frazer S, Gehlenborg N, Heiman DI, Lin P, Liu Y, Stojanov P, Voet D, Zhang H, Zou L, Chin L, Getz G, Bernard B, Kreisberg D, Reynolds S, Rovira H, Shmulevich I, Ramirez R, Schultz N, Gao J, Jacobsen A, Aksoy BA, Antipin Y, Ciriello G, Dresdner G, Gross B, Lee W, Reva B, Shen R, Sinha R, Sumer SO, Weinhold N, Ladanyi M, Sander C, Benz C, Carlin D, Haussler D, Ng S, Paull EO, Stuart J, Zhu J, Liu Y, Zhang W, Taylor BS, Lichtenberg TM, Zmuda E, Barr T, Black AD, George M, Hanf B, Helsel C, McAllister C, Ramirez NC, Tabler TR, Weaver S, Wise L, Bowen J, Gastier-Foster JM, Weinstein JN, Lerner S, Jian W, Tello S, Ittman M, Castro P, McClenden WD, Morgan M, Gibbs R, Liu Y, Saller C, Tarvin K, DiPiero JM, Owens J, Bollag R, Li Q, Weinberger P, Czerwinski C, Huelsenbeck-Dill L, Iacocca M, Petrelli N, Rabeno B, Swanson P, Shelton T, Curley E, Gardner J, Mallery D, Penny R, Van Bang N, Thi Hanh P, Kohl B, Van Le X, Duc Phu B, Thorp R, Viet Tien N, Quang Vinh L, Sandusky G, Burks E, Christ K, Gee J, Holway A, Moinzadeh A, Sorcini A, Sullivan T, Al-Ahmadie HA, Bajorin DF, Bochner BH, Garcia-Grossman IR, Regazzi AM, Solit DB, Rosenberg JE, Reuter VE, Koppie T, Boice L, Kimryn Rathmell W, Thorne L, Bastacky S, Davies B, Dhir R, Gingrich J, Hrebinko R, Maranchie J, Nelson J, Parwani A, Bshara W, Gaudioso C, Morrison C, Alexopoulou V, Bartlett J, Engel J, Kodeeswaran S, Antic T, O'Donnell PH, Smith ND, Steinberg GD, Egea S, Gomez-Fernandez C, Herbert L, Jorda M, Soloway M, Beaver A, Carter S, Kapur P, Lewis C, Lotan Y, Robinson B, Hansel D, Guo C, Bondaruk J, Czerniak B, Akbani R, Broom BM, Liu Y, Zhang W, Weinstein JN, Lerner S, Morgan M, Kim J, Cherniack AD, Freeman SS, Sekhar Pedamallu C, Noble MS, Kwiatkowski DJ, Al-Ahmadie HA, Bajorin DF, Bochner BH, Solit DB, Rosenberg JE, Reuter VE, Koppie T, Robinson B, Skinner E, Ramirez R, Schultz N, Hansel D, Kim WY, Guo C, Bondaruk J, Aldape K, Czerniak B, Jensen MA, Kahn AB, Pihl TD, Pot DA, Srinivasan D, Wan Y, Ferguson ML, Zenklusen JC, Davidsen T, Demchok JA, Mills Shaw KR, Sheth M, Tarnuzzer R, Wang Z, Yang L, Hutter C, Ozenberger BA, Sofia HJ, Eley G.

Abstract

Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.

PMID:
24476821
PMCID:
PMC3962515
DOI:
10.1038/nature12965
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances, Grant support

Publication type

MeSH terms

Substances

Grant support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center