화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Nature, Vol.499, No.7456, 43-43, 2013
DOI10.1038/nature12222  Export Citation
Comprehensivemolecular characterization of clear cell renal cell carcinoma
Creighton CJ, Morgan M, Gunaratne PH, Wheeler DA, Gibbs RA, Robertson AG, Chu A, Beroukhim R, Cibulskis K, Signoretti S, Vandin F, Wu HT, Raphael BJ, Verhaak RGW, Tamboli P, Torres-Garcia W, Akbani R, Weinstein JN, Reuter V, Hsieh JJ, Brannon AR, Hakimi AA, Jacobsen A, Ciriello G, Reva B, Ricketts CJ, Linehan WM, Stuart JM, Rathmell WK, Shen H, Laird PW, Muzny D, Davis C, Morgan M, Xi L, Chang K, Kakkar N, Trevino LR, Benton S, Reid JG, Morton D, Doddapaneni H, Han Y, Lewis L, Dinh H, Kovar C, Zhu YM, Santibanez J, Wang M, Hale W, Kalra D, Creighton CJ, Wheeler DA, Gibbs RA, Getz G, Cibulskis K, Lawrence MS, Sougnez C, Carter SL, Sivachenko A, Lichtenstein L, Stewart C, Voet D, Fisher S, Gabriel SB, Lander E, Beroukhim R, Schumacher SE, Tabak B, Saksena G, Onofrio RC, Carter SL, Cherniack AD, Gentry J, Ardlie K, Sougnez C, Getz G, Gabriel SB, Meyerson M, Robertson AG, Chu AD, Chun HJE, Mungall AJ, Sipahimalani P, Stoll D, Ally A, Balasundaram M, Butterfield YSN, Carlsen R, Carter C, Chuah E, Coope RJN, Dhalla N, Gorski S, Guin R, Hirst C, Hirst M, Holt RA, Lebovitz C, Lee D, Li HYI, Mayo M, Moore RA, Pleasance E, Plettner P, Schein JE, Shafiei A, Slobodan JR, Tam A, Thiessen N, Varhol RJ, Wye N, Zhao YJ, Birol I, Jones SJM, Marra MA, Auman JT, Tan DH, Jones CD, Hoadley KA, Mieczkowski PA, Mose LE, Jefferys SR, Topal M, Liquori C, Turman YJ, Shi Y, Waring S, Buda E, Walsh J, Wu JY, Bodenheimer T, Hoyle AP, Simons JV, Soloway M, Balu S, Parker JS, Hayes DN, Perou CM, Kucherlapati R, Park P, Shen H, Triche T, Weisenberger DJ, Lai PH, Bootwalla MS, Maglinte DT, Mahurkar S, Berman BP, Van den Berg DJ, Cope L, Baylin SB, Laird PW, Creighton CJ, Wheeler DA, Getz G, Noble MS, DiCara D, Zhang HL, Cho J, Heiman DI, Gehlenborg N, Voet D, Mallard W, Lin P, Frazer S, Stojanov P, Liu YC, Zhou LH, Kim J, Lawrence MS, Chin L, Vandin F, Wu HT, Raphael BJ, Benz C, Yau C, Reynolds SM, Shmulevich I, Verhaak RGW, Torres-Garcia W, Vegesna R, Kim H, Zhang W, Cogdell D, Jonasch E, Ding ZY, Lu YL, Akbani R, Zhang NX, Unruh AK, Casasent TD, Wakefield C, Tsavachidou D, Chin L, Mills GB, Weinstein JN, Jacobsen A, Brannon AR, Ciriello G, Schultz N, Hakimi AA, Reva B, Antipin Y, Gao JJ, Cerami E, Gross B, Aksoy BA, Sinha R, Weinhold N, Sumer SO, Taylor BS, Shen RL, Ostrovnaya I, Hsieh JJ, Berger MF, Ladanyi M, Sander C, Fei SS, Stout A, Spellman PT, Rubin DL, Liu TT, Stuart JM, Ng S, Paull EO, Carlin D, Goldstein T, Waltman P, Ellrott K, Zhu J, Haussler D, Gunaratne PH, Xiao WM, Shelton C, Gardner J, Penny R, Sherman M, Mallery D, Morris S, Paulauskis J, Burnett K, Shelton T, Signoretti S, Kaelin WG, Choueiri T, Atkins MB, Penny R, Burnett K, Mallery D, Curley E, Tickoo S, Reuter V, Rathmell WK, Thorne L, Boice L, Huang M, Fisher JC, Linehan WM, Vocke CD, Peterson J, Worrell R, Merino MJ, Schmidt LS, Tamboli P, Czerniak BA, Aldape KD, Wood CG, Boyd J, Weaver J, Iacocca MV, 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 LA, Bshara W, Gaudioso C, Morrison C, Dhir R, Maranchie J, Nelson J, Parwani A, Potapova O, Fedosenko K, Cheville JC, Thompson RH, Signoretti S, Kaelin WG, Atkins MB, Tickoo S, Reuter V, Linehan WM, Vocke CD, Peterson J, Merino MJ, Schmidt LS, Tamboli P, Mosquera JM, Rubin MA, Blute ML, Rathmell WK, 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 JA, Davidsen T, Wang ZN, Yang LM, Tarnuzzer RW, Zhang JS, Eley G, Ferguson ML, Shaw KRM, Guyer MS, Ozenberger BA, Sofia HJ
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.