Comprehensive molecular characterization of urothelial bladder carcinoma.
Details
Serval ID
serval:BIB_0D73895A86B1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Comprehensive molecular characterization of urothelial bladder carcinoma.
Journal
Nature
Working group(s)
Cancer Genome Atlas Research Network
Contributor(s)
Weinstein J.N., Akbani R., Broom B.M., Wang W., Verhaak R.G., McConkey D., Lerner S., Morgan M., Creighton C.J., Smith C., Kwiatkowski D.J., Cherniack A.D., Kim J., Sekhar Pedamallu C., Noble M.S., Al-Ahmadie H.A., Reuter V.E., Rosenberg J.E., Bajorin D.F., Bochner B.H., Solit D.B., Koppie T., Robinson B., Gordenin D.A., Fargo D., Klimczak L.J., Roberts S.A., Au J., Laird P.W., Hinoue T., Schultz N., Ramirez R., Hansel D., Hoadley K.A., Kim W.Y., Damrauer J.S., Baylin S.B., Mungall A.J., Robertson A.G., Chu A., Kwiatkowski D.J., Sougnez C., Cibulskis K., Lichtenstein L., Sivachenko A., Stewart C., Lawrence M.S., Getz G., Lander E., Gabriel S.B., Creighton C.J., Donehower L., Cherniack A.D., Kim J., Carter S.L., Saksena G., Schumacher S.E., Sougnez C., Freeman S.S., Jung J., Sekhar Pedamallu C., Bhatt A.S., Pugh T., Getz G., Beroukhim R., Gabriel S.B., Meyerson M., Mungall A.J., Robertson A.G., Chu A., Ally A., Balasundaram M., Butterfield Y.S., Dhalla N., Hirst C., Holt R.A., Jones S.J., Lee D., Li H.I., Marra M.A., Mayo M., Moore R.A., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Wong T., Wye N., Bowlby R., Chuah E., Guin R., Jones S.J., Marra M.A., Hinoue T., Shen H., Bootwalla M.S., Triche T., Lai P.H., Van Den Berg D.J., Weisenberger D.J., Laird P.W., Hansel D., Hoadley K.A., Balu S., Bodenheimer T., Damrauer J.S., Hoyle A.P., Jefferys S.R., Meng S., Mose L.E., Simons J.V., Soloway M.G., Wu J., Kim W.Y., Parker J.S., Hayes D.N., Roach J., Buda E., Jones C.D., Mieczkowski P.A., Tan D., Veluvolu U., Waring S., Auman J.T., Perou C.M., Wilkerson M.D., Santoso N., Parfenov M., Ren X., Pantazi A., Hadjipanayis A., Seidman J., Kucherlapati R., Lee S., Yang L., Park P.J., Baylin S.B., Wei Xu A., Protopopov A., Zhang J., Bristow C., Mahadeshwar H.S., Seth S., Song X., Tang J., Zeng D., Chin L., Guo C., Weinstein J.N., Akbani R., Broom B.M., McConkey D., Casasent T.D., Liu W., Ju Z., Motter T., Peng B., Ryan M., Wang W., Verhaak R.G., Su X., Yang J.Y., Lorenzi P.L., Yao H., Zhang N., Zhang J., Mills G.B., Kim J., Noble M.S., Cho J., DiCara D., Frazer S., Gehlenborg N., Heiman D.I., 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 B.A., Antipin Y., Ciriello G., Dresdner G., Gross B., Lee W., Reva B., Shen R., Sinha R., Sumer S.O., Weinhold N., Ladanyi M., Sander C., Benz C., Carlin D., Haussler D., Ng S., Paull E.O., Stuart J., Zhu J., Liu Y., Zhang W., Taylor B.S., Lichtenberg T.M., Zmuda E., Barr T., Black A.D., George M., Hanf B., Helsel C., McAllister C., Ramirez N.C., Tabler T.R., Weaver S., Wise L., Bowen J., Gastier-Foster J.M., Weinstein J.N., Lerner S., Jian W., Tello S., Ittman M., Castro P., McClenden W.D., Morgan M., Gibbs R., Liu Y., Saller C., Tarvin K., DiPiero J.M., 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 H.A., Bajorin D.F., Bochner B.H., Garcia-Grossman I.R., Regazzi A.M., Solit D.B., Rosenberg J.E., Reuter V.E., 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 P.H., Smith N.D., Steinberg G.D., 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 B.M., Liu Y., Zhang W., Weinstein J.N., Lerner S., Morgan M., Kim J., Cherniack A.D., Freeman S.S., Sekhar Pedamallu C., Noble M.S., Kwiatkowski D.J., Al-Ahmadie H.A., Bajorin D.F., Bochner B.H., Solit D.B., Rosenberg J.E., Reuter V.E., Koppie T., Robinson B., Skinner E., Ramirez R., Schultz N., Hansel D., Kim W.Y., Guo C., Bondaruk J., Aldape K., Czerniak B., Jensen M.A., Kahn A.B., Pihl T.D., Pot D.A., Srinivasan D., Wan Y., Ferguson M.L., Zenklusen J.C., Davidsen T., Demchok J.A., Mills Shaw K.R., Sheth M., Tarnuzzer R., Wang Z., Yang L., Hutter C., Ozenberger B.A., Sofia H.J., Eley G.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
20/03/2014
Peer-reviewed
Oui
Volume
507
Number
7492
Pages
315-322
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Publication Status: ppublish
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.
Keywords
Cell Cycle/genetics, Chromatin/genetics, Chromatin/virology, Down-Regulation/genetics, Gene Expression Regulation, Neoplastic/genetics, Humans, MicroRNAs/genetics, MicroRNAs/metabolism, Molecular Targeted Therapy, Oxidative Stress/genetics, Phosphatidylinositol 3-Kinases/metabolism, Protein Kinases/genetics, Protein Kinases/metabolism, Proto-Oncogene Proteins c-akt/metabolism, RNA, Messenger/genetics, RNA, Messenger/metabolism, Signal Transduction/genetics, TOR Serine-Threonine Kinases/metabolism, Urinary Bladder Neoplasms/drug therapy, Urinary Bladder Neoplasms/genetics, Urinary Bladder Neoplasms/pathology, Urinary Bladder Neoplasms/virology, Virus Integration/genetics
Pubmed
Web of science
Open Access
Yes
Create date
13/11/2018 10:30
Last modification date
20/08/2019 13:34
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