Synapse - Comprehensive molecular characterization of clear cell renal cell carcinoma

Comprehensive molecular characterization of clear cell renal cell carcinoma Journal Article

Authors:	Creighton, C. J.; Morgan, M.; Gunaratne, P. H.; Wheeler, D. A.; Gibbs, R. A.; Robertson, G.; Chu, A.; Beroukhim, R.; Cibulskis, K.; Signoretti, S.; Vandin, F.; Wu, H. T.; Raphael, B. J.; Verhaak, R. G. W.; Tamboli, P.; Torres-Garcia, W.; Akbani, R.; Weinstein, J. N.; Reuter, V.; Hsieh, J. J.; Brannon, A. R.; Hakimi, A. A.; Jacobsen, A.; Ciriello, G.; Reva, B.; Ricketts, C. J.; Linehan, W. M.; Stuart, J. M.; Rathmell, W. K.; Hui, S.; Laird, P. W.; Muzny, D.; Davis, C.; Liu, X.; Chang, K.; Kakkar, N.; Trevino, L. R.; Benton, S.; Reid, J. G.; Morton, D.; Doddapaneni, H.; Yi, H.; Lewis, L.; Huyen, D.; Kovar, C.; Zhu, Y.; Santibanez, J.; Min, W.; Hale, W.; Kalra, D.; Getz, G.; Lawrence, M. S.; Sougnez, C.; Carter, S. L.; Sivachenko, A.; Lee, L.; Stewart, C.; Voet, D.; Fisher, S.; Gabriel, S. B.; Lander, E.; Schumacher, S. E.; Tabak, B.; Saksena, G.; Onofrio, R. C.; Cherniack, A. D.; Gentry, J.; Ardlie, K.; Meyerson, M.; Chun, H. J. E.; Mungall, A. J.; Sipahimalani, P.; Stoll, D.; Ally, A.; Balasundaram, M.; Butterfield, Y. S. N.; Carlsen, R.; Carter, C.; Chuah, E.; Coope, R. J. N.; 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.; Berger, M. F.; Tickoo, S.; Ladanyi, M.; Schultz, N.; Antipin, Y.; Sander, C.; Ostrovnaya, I.; Gao, J.; Shen, R.; Cerami, E.; Gross, B.; Aksoy, B. A.; Sinha, R.; Weinhold, N.; Sumer, S. O.; Taylor, B. S.
Article Title:	Comprehensive molecular characterization of clear cell renal cell carcinoma
Abstract:	Genetic changes underlying clear cell renal cell carcinoma(ccRCC) include alterations in genes controlling cellularoxygen 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, decreasedAMPK 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. © 2013 Macmillan Publishers Limited. All rights reserved.
Journal Title:	Nature
Volume:	499
Issue:	7456
ISSN:	0028-0836
Publisher:	Nature Publishing Group
Date Published:	2013-07-04
Start Page:	43
End Page:	49
Language:	English
DOI:	10.1038/nature12222
PROVIDER:	scopus
PMCID:	PMC3771322
PUBMED:	23792563
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84879890360&partnerID=40&md5=33c7aaff4c78e94c5a80ba7b307cc194
Notes:	--- - Cited By (since 1996):1 - "Export Date: 25 September 2013" - "CODEN: NATUA" - "Source: Scopus"