Comprehensive molecular characterization of clear cell renal cell carcinoma.
Details
Serval ID
serval:BIB_4DE3562D2B02
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Comprehensive molecular characterization of clear cell renal cell carcinoma.
Journal
Nature
Working group(s)
Cancer Genome Atlas Research Network
Contributor(s)
Creighton C.J., Morgan M., Gunaratne P.H., Wheeler D.A., Gibbs R.A., Robertson A., Chu A., Beroukhim R., Cibulskis K., Signoretti S., Vandin F., Wu H.T., Raphael B.J., Verhaak R.G., Tamboli P., Torres-Garcia W., Akbani R., Weinstein J.N., Reuter V., Hsieh J.J., Brannon A., Hakimi A., Jacobsen A., Ciriello G., Reva B., Ricketts C.J., Linehan W., Stuart J.M., Rathmell W., Shen H., Laird P.W., Muzny D., Davis C., Morgan M., Xi L., Chang K., Kakkar N., Treviño L.R., Benton S., Reid J.G., Morton D., Doddapaneni H., Han Y., Lewis L., Dinh H., Kovar C., Zhu Y., Santibanez J., Wang M., Hale W., Kalra D., Creighton C.J., Wheeler D.A., Gibbs R.A., Getz G., Cibulskis K., Lawrence M.S., Sougnez C., Carter S.L., Sivachenko A., Lichtenstein L., Stewart C., Voet D., Fisher S., Gabriel S.B., Lander E., Beroukhim R., Schumacher S.E., Tabak B., Saksena G., Onofrio R.C., Carter S.L., Cherniack A.D., Gentry J., Ardlie K., Sougnez C., Getz G., Gabriel S.B., Meyerson M., Robertson A., Chu A., Chun H.J., Mungall A.J., Sipahimalani P., Stoll D., Ally A., Balasundaram M., Butterfield Y.S., Carlsen R., Carter C., Chuah E., Coope R.J., Dhalla N., Gorski S., Guin R., Hirst C., Hirst M., Holt R.A., Lebovitz C., Lee D., Li H.I., Mayo M., Moore R.A., Pleasance E., Plettner P., Schein J.E., Shafiei A., Slobodan J.R., Tam A., Thiessen N., Varhol R.J., Wye N., Zhao Y., Birol I., Jones S.J., Marra M.A., Auman J.T., Tan D., Jones C.D., Hoadley K.A., Mieczkowski P.A., Mose L.E., Jefferys S.R., Topal M.D., Liquori C., Turman Y.J., Shi Y., Waring S., Buda E., Walsh J., Wu J., Bodenheimer T., Hoyle A.P., Simons J.V., Soloway M.G., Balu S., Parker J.S., Hayes D., Perou C.M., Kucherlapati R., Park P., Shen H., Triche T., Weisenberger D.J., Lai P.H., Bootwalla M.S., Maglinte D.T., Mahurkar S., Berman B.P., Van Den Berg D.J., Cope L., Baylin S.B., Laird P.W., Creighton C.J., Wheeler D.A., Getz G., Noble M.S., DiCara D., Zhang H., Cho J., Heiman D.I., Gehlenborg N., Voet D., Mallard W., Lin P., Frazer S., Stojanov P., Liu Y., Zhou L., Kim J., Lawrence M.S., Chin L., Vandin F., Wu H.T., Raphael B.J., Benz C., Yau C., Reynolds S.M., Shmulevich I., Verhaak R.G., Torres-Garcia W., Vegesna R., Kim H., Zhang W., Cogdell D., Jonasch E., Ding Z., Lu Y., Akbani R., Zhang N., Unruh A.K., Casasent T.D., Wakefield C., Tsavachidou D., Chin L., Mills G.B., Weinstein J.N., Jacobsen A., Brannon R., Ciriello G., Schultz N., Hakimi A., Reva B., Antipin Y., Gao J., Cerami E., Gross B., Aksoy B.A., Sinha R., Weinhold N., Sumer S., Taylor B.S., Shen R., Ostrovnaya I., Hsieh J.J., Berger M.F., Ladanyi M., Sander C., Fei S.S., Stout A., Spellman P.T., Rubin D.L., Liu T.T., Stuart J.M., Ng S., Paull E.O., Carlin D., Goldstein T., Waltman P., Ellrott K., Zhu J., Haussler D., Gunaratne P.H., Xiao W., Shelton C., Gardner J., Penny R., Sherman M., Mallery D., Morris S., Paulauskis J., Burnett K., Shelton T., Signoretti S., Kaelin W.G., Choueiri T., Atkins M.B., Penny R., Burnett K., Mallery D., Curley E., Tickoo S., Reuter V., Rathmell W., Thorne L., Boice L., Huang M., Fisher J.C., Linehan W.M., Vocke C.D., Peterson J., Worrell R., Merino M.J., Schmidt L.S., Tamboli P., Czerniak B.A., Aldape K.D., Wood C.G., Boyd J., Weaver J., Iacocca M.V., Petrelli N., Witkin G., Brown J., Czerwinski C., Huelsenbeck-Dill L., Rabeno B., Myers J., Morrison C., Bergsten J., Eckman J., Harr J., Smith C., Tucker K., Zach L.A., Bshara W., Gaudioso C., Morrison C., Dhir R., Maranchie J., Nelson J., Parwani A., Potapova O., Fedosenko K., Cheville J.C., Thompson R.H., Signoretti S., Kaelin W.G., Atkins M.B., Tickoo S., Reuter V., Linehan W.M., Vocke C.D., Peterson J., Merino M.J., Schmidt L.S., Tamboli P., Mosquera J.M., Rubin M.A., Blute M.L., Rathmell W., Pihl T., Jensen M., Sfeir R., Kahn A., Chu A., Kothiyal P., Snyder E., Pontius J., Ayala B., Backus M., Walton J., Baboud J., Berton D., Nicholls M., Srinivasan D., Raman R., Girshik S., Kigonya P., Alonso S., Sanbhadti R., Barletta S., Pot D., Sheth M., Demchok J.A., Davidsen T., Wang Z., Yang L., Tarnuzzer R.W., Zhang J., Eley G., Ferguson M.L., Mills Shaw K.R., Guyer M.S., Ozenberger B.A., Sofia H.J.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
04/07/2013
Peer-reviewed
Oui
Volume
499
Number
7456
Pages
43-49
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
Keywords
AMP-Activated Protein Kinases/metabolism, Acetyl-CoA Carboxylase/metabolism, Carcinoma, Renal Cell/classification, Carcinoma, Renal Cell/genetics, Carcinoma, Renal Cell/metabolism, Carcinoma, Renal Cell/pathology, Chromatin/genetics, Chromatin/metabolism, Chromatin Assembly and Disassembly/genetics, Citric Acid Cycle/genetics, DNA Methylation/genetics, DNA Mutational Analysis, Epigenesis, Genetic/genetics, GRB10 Adaptor Protein/genetics, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genome, Human/genetics, Genomics, Histone-Lysine N-Methyltransferase/genetics, Histone-Lysine N-Methyltransferase/metabolism, Humans, Metabolic Networks and Pathways/genetics, MicroRNAs/genetics, Mutation, PTEN Phosphohydrolase/metabolism, Pentose Phosphate Pathway/genetics, Phosphatidylinositol 3-Kinases/metabolism, Proto-Oncogene Proteins c-akt/metabolism, RNA, Neoplasm/analysis, RNA, Neoplasm/genetics, Signal Transduction/genetics, Survival Analysis
Pubmed
Web of science
Open Access
Yes
Create date
06/07/2018 12:02
Last modification date
20/08/2019 15:03
Usage data
