Comprehensivemolecular characterization of clear cell renal cell carcinoma

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 sig...

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Main Authors:	Creighton, C., Morgan, M., Gunaratne, P., Wheeler, D., Gibbs, R., Robertson, A., Chu, A., Beroukhim, R., Cibulskis, K., Signoretti, S., Vandin, F., Wu, H., Raphael, B., Verhaak, R., Tamboli, P., Torres-Garcia, W., Akbani, R., Weinstein, J., Reuter, V., Hsieh, J., Brannon, A., Hakimi, A., Jacobsen, A., Ciriello, G., Reva, B., Ricketts, C., Linehan, W., Stuart, J., Rathmell, W., Shen, H., Laird, P., Muzny, D., Davis, C., Xi, L., Chang, K., Kakkar, N., Trevino, L., Benton, S., Reid, J., Morton, D., Doddapaneni, H., Han, Y., Lewis, L., Dinh, H., Kovar, C., Zhu, Y., Santibanez, J., Wang, M., Hale, W., Kalra, D., Getz, G., Lawrence, M., Sougnez, C., Carter, S., Sivachenko, A., Lichtenstein, L., Stewart, C., Voet, D., Fisher, S., Gabriel, S., Lander, E., Schumacher, S., Tabak, B., Saksena, G., Onofrio, R., Cherniack, A., Gentry, J., Ardlie, K., Meyerson, M., Chun, H., Mungall, A., Sipahimalani, P., Stoll, D., Ally, A., Balasundaram, M., Butterfield, Y., Carlsen, R., Carter, C., Chuah, E., Coope, R., Dhalla, N., Gorski, S., Guin, R., Hirst, C., Hirst, M., Holt, R., Lebovitz, C., Lee, D., Li, H., Mayo, M., Moore, R., Pleasance, E., Plettner, P., Schein, J., Shafiei, A., Slobodan, J., Tam, A., Thiessen, N., Varhol, Richard, Wye, N., Zhao, Y., Birol, I., Jones, S., Marra, M., Auman, J., Tan, D., Jones, C., Hoadley, K., Mieczkowski, P., Mose, L., Jefferys, S., Topal, M., Liquori, C., Turman, Y., Shi, Y., Waring, S., Buda, E., Walsh, J., Wu, J., Bodenheimer, T., Hoyle, A., Simons, J., Soloway, M., Balu, S., Parker, J., Hayes, D., Perou, C., Kucherlapati, R., Park, P., Triche, T., Weisenberger, D., Lai, P., Bootwalla, M., Maglinte, D., Mahurkar, S., Berman, B., Van den Berg, D., Cope, L., Baylin, S., Noble, M., DiCara, D., Zhang, H., Cho, J., Heiman, D., Gehlenborg, N., Mallard, W., Lin, P., Frazer, S., Stojanov, P., Liu, Y., Zhou, L., Kim, J., Chin, L., Benz, C., Yau, C., Reynolds, S., Shmulevich, I., Vegesna, R., Kim, H., Zhang, W., Cogdell, D., Jonasch, E., Ding, Z., Lu, Y., Zhang, N., Unruh, A., Casasent, T., Wakefield, C., Tsavachidou, D., Mills, G., Schultz, N., Antipin, Y., Gao, J., Cerami, E., Gross, B., Aksoy, B., Sinha, R., Weinhold, N., Sumer, S., Taylor, B., Shen, R., Ostrovnaya, I., Berger, M., Ladanyi, M., Sander, C., Fei, S., Stout, A., Spellman, P., Rubin, D., Liu, T., Sam, N., Paull, E., Carlin, D., Goldstein, T., Waltman, P., Ellrott, K., Zhu, J., Haussler, D., Xiao, W., Shelton, C., Gardner, J., Penny, R., Sherman, M., Mallery, D., Morris, S., Paulauskis, J., Burnett, K., Shelton, T., Kaelin, W., Choueiri, T., Atkins, M., Curley, E., Tickoo, S., Thorne, L., Boice, L., Huang, M., Fisher, J., Vocke, C., Peterson, J., Worrell, R., Merino, M., Schmidt, L., Czerniak, B., Aldape, K., Wood, C., Boyd, J., Weaver, J., Iacocca, M., 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., Bshara, W., Gaudioso, C., Dhir, R., Maranchie, J., Nelson, J., Parwani, A., Potapova, O., Fedosenko, K., Cheville, J., Thompson, R., Mosquera, J., Rubin, M., Blute, M., Pihl, T., Jensen, M., Sfeir, R., Kahn, 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., Davidsen, T., Wang, Z., Yang, L., Tarnuzzer, R., Zhang, J., Eley, G., Ferguson, M., Shaw, K., Guyer, M., Ozenberger, B., Sofia, H.
Format:	Journal Article
Published:	Nature Publishing Group 2013
Online Access:	http://hdl.handle.net/20.500.11937/66477

_version_	1848761331092553728
author	Creighton, C. Morgan, M. Gunaratne, P. Wheeler, D. Gibbs, R. Robertson, A. Chu, A. Beroukhim, R. Cibulskis, K. Signoretti, S. Vandin, F. Wu, H. Raphael, B. Verhaak, R. Tamboli, P. Torres-Garcia, W. Akbani, R. Weinstein, J. Reuter, V. Hsieh, J. Brannon, A. Hakimi, A. Jacobsen, A. Ciriello, G. Reva, B. Ricketts, C. Linehan, W. Stuart, J. Rathmell, W. Shen, H. Laird, P. Muzny, D. Davis, C. Morgan, M. Xi, L. Chang, K. Kakkar, N. Trevino, L. Benton, S. Reid, J. Morton, D. Doddapaneni, H. Han, Y. Lewis, L. Dinh, H. Kovar, C. Zhu, Y. Santibanez, J. Wang, M. Hale, W. Kalra, D. Creighton, C. Wheeler, D. Gibbs, R. Getz, G. Cibulskis, K. Lawrence, M. Sougnez, C. Carter, S. Sivachenko, A. Lichtenstein, L. Stewart, C. Voet, D. Fisher, S. Gabriel, S. Lander, E. Beroukhim, R. Schumacher, S. Tabak, B. Saksena, G. Onofrio, R. Carter, S. Cherniack, A. Gentry, J. Ardlie, K. Sougnez, C. Getz, G. Gabriel, S. Meyerson, M. Robertson, A. Chu, A. Chun, H. Mungall, A. Sipahimalani, P. Stoll, D. Ally, A. Balasundaram, M. Butterfield, Y. Carlsen, R. Carter, C. Chuah, E. Coope, R. Dhalla, N. Gorski, S. Guin, R. Hirst, C. Hirst, M. Holt, R. Lebovitz, C. Lee, D. Li, H. Mayo, M. Moore, R. Pleasance, E. Plettner, P. Schein, J. Shafiei, A. Slobodan, J. Tam, A. Thiessen, N. Varhol, Richard Wye, N. Zhao, Y. Birol, I. Jones, S. Marra, M. Auman, J. Tan, D. Jones, C. Hoadley, K. Mieczkowski, P. Mose, L. Jefferys, S. Topal, M. Liquori, C. Turman, Y. Shi, Y. Waring, S. Buda, E. Walsh, J. Wu, J. Bodenheimer, T. Hoyle, A. Simons, J. Soloway, M. Balu, S. Parker, J. Hayes, D. Perou, C. Kucherlapati, R. Park, P. Shen, H. Triche, T. Weisenberger, D. Lai, P. Bootwalla, M. Maglinte, D. Mahurkar, S. Berman, B. Van den Berg, D. Cope, L. Baylin, S. Laird, P. Creighton, C. Wheeler, D. Getz, G. Noble, M. DiCara, D. Zhang, H. Cho, J. Heiman, D. Gehlenborg, N. Voet, D. Mallard, W. Lin, P. Frazer, S. Stojanov, P. Liu, Y. Zhou, L. Kim, J. Lawrence, M. Chin, L. Vandin, F. Wu, H. Raphael, B. Benz, C. Yau, C. Reynolds, S. Shmulevich, I. Verhaak, R. Torres-Garcia, W. Vegesna, R. Kim, H. Zhang, W. Cogdell, D. Jonasch, E. Ding, Z. Lu, Y. Akbani, R. Zhang, N. Unruh, A. Casasent, T. Wakefield, C. Tsavachidou, D. Chin, L. Mills, G. Weinstein, J. Jacobsen, A. Brannon, A. Ciriello, G. Schultz, N. Hakimi, A. Reva, B. Antipin, Y. Gao, J. Cerami, E. Gross, B. Aksoy, B. Sinha, R. Weinhold, N. Sumer, S. Taylor, B. Shen, R. Ostrovnaya, I. Hsieh, J. Berger, M. Ladanyi, M. Sander, C. Fei, S. Stout, A. Spellman, P. Rubin, D. Liu, T. Stuart, J. Sam, N. Paull, E. Carlin, D. Goldstein, T. Waltman, P. Ellrott, K. Zhu, J. Haussler, D. Gunaratne, P. Xiao, W. Shelton, C. Gardner, J. Penny, R. Sherman, M. Mallery, D. Morris, S. Paulauskis, J. Burnett, K. Shelton, T. Signoretti, S. Kaelin, W. Choueiri, T. Atkins, M. Penny, R. Burnett, K. Mallery, D. Curley, E. Tickoo, S. Reuter, V. Rathmell, W. Thorne, L. Boice, L. Huang, M. Fisher, J. Linehan, W. Vocke, C. Peterson, J. Worrell, R. Merino, M. Schmidt, L. Tamboli, P. Czerniak, B. Aldape, K. Wood, C. Boyd, J. Weaver, J. Iacocca, M. 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. Bshara, W. Gaudioso, C. Morrison, C. Dhir, R. Maranchie, J. Nelson, J. Parwani, A. Potapova, O. Fedosenko, K. Cheville, J. Thompson, R. Signoretti, S. Kaelin, W. Atkins, M. Tickoo, S. Reuter, V. Linehan, W. Vocke, C. Peterson, J. Merino, M. Schmidt, L. Tamboli, P. Mosquera, J. Rubin, M. Blute, M. 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. Davidsen, T. Wang, Z. Yang, L. Tarnuzzer, R. Zhang, J. Eley, G. Ferguson, M. Shaw, K. Guyer, M. Ozenberger, B. Sofia, H.
author_facet	Creighton, C. Morgan, M. Gunaratne, P. Wheeler, D. Gibbs, R. Robertson, A. Chu, A. Beroukhim, R. Cibulskis, K. Signoretti, S. Vandin, F. Wu, H. Raphael, B. Verhaak, R. Tamboli, P. Torres-Garcia, W. Akbani, R. Weinstein, J. Reuter, V. Hsieh, J. Brannon, A. Hakimi, A. Jacobsen, A. Ciriello, G. Reva, B. Ricketts, C. Linehan, W. Stuart, J. Rathmell, W. Shen, H. Laird, P. Muzny, D. Davis, C. Morgan, M. Xi, L. Chang, K. Kakkar, N. Trevino, L. Benton, S. Reid, J. Morton, D. Doddapaneni, H. Han, Y. Lewis, L. Dinh, H. Kovar, C. Zhu, Y. Santibanez, J. Wang, M. Hale, W. Kalra, D. Creighton, C. Wheeler, D. Gibbs, R. Getz, G. Cibulskis, K. Lawrence, M. Sougnez, C. Carter, S. Sivachenko, A. Lichtenstein, L. Stewart, C. Voet, D. Fisher, S. Gabriel, S. Lander, E. Beroukhim, R. Schumacher, S. Tabak, B. Saksena, G. Onofrio, R. Carter, S. Cherniack, A. Gentry, J. Ardlie, K. Sougnez, C. Getz, G. Gabriel, S. Meyerson, M. Robertson, A. Chu, A. Chun, H. Mungall, A. Sipahimalani, P. Stoll, D. Ally, A. Balasundaram, M. Butterfield, Y. Carlsen, R. Carter, C. Chuah, E. Coope, R. Dhalla, N. Gorski, S. Guin, R. Hirst, C. Hirst, M. Holt, R. Lebovitz, C. Lee, D. Li, H. Mayo, M. Moore, R. Pleasance, E. Plettner, P. Schein, J. Shafiei, A. Slobodan, J. Tam, A. Thiessen, N. Varhol, Richard Wye, N. Zhao, Y. Birol, I. Jones, S. Marra, M. Auman, J. Tan, D. Jones, C. Hoadley, K. Mieczkowski, P. Mose, L. Jefferys, S. Topal, M. Liquori, C. Turman, Y. Shi, Y. Waring, S. Buda, E. Walsh, J. Wu, J. Bodenheimer, T. Hoyle, A. Simons, J. Soloway, M. Balu, S. Parker, J. Hayes, D. Perou, C. Kucherlapati, R. Park, P. Shen, H. Triche, T. Weisenberger, D. Lai, P. Bootwalla, M. Maglinte, D. Mahurkar, S. Berman, B. Van den Berg, D. Cope, L. Baylin, S. Laird, P. Creighton, C. Wheeler, D. Getz, G. Noble, M. DiCara, D. Zhang, H. Cho, J. Heiman, D. Gehlenborg, N. Voet, D. Mallard, W. Lin, P. Frazer, S. Stojanov, P. Liu, Y. Zhou, L. Kim, J. Lawrence, M. Chin, L. Vandin, F. Wu, H. Raphael, B. Benz, C. Yau, C. Reynolds, S. Shmulevich, I. Verhaak, R. Torres-Garcia, W. Vegesna, R. Kim, H. Zhang, W. Cogdell, D. Jonasch, E. Ding, Z. Lu, Y. Akbani, R. Zhang, N. Unruh, A. Casasent, T. Wakefield, C. Tsavachidou, D. Chin, L. Mills, G. Weinstein, J. Jacobsen, A. Brannon, A. Ciriello, G. Schultz, N. Hakimi, A. Reva, B. Antipin, Y. Gao, J. Cerami, E. Gross, B. Aksoy, B. Sinha, R. Weinhold, N. Sumer, S. Taylor, B. Shen, R. Ostrovnaya, I. Hsieh, J. Berger, M. Ladanyi, M. Sander, C. Fei, S. Stout, A. Spellman, P. Rubin, D. Liu, T. Stuart, J. Sam, N. Paull, E. Carlin, D. Goldstein, T. Waltman, P. Ellrott, K. Zhu, J. Haussler, D. Gunaratne, P. Xiao, W. Shelton, C. Gardner, J. Penny, R. Sherman, M. Mallery, D. Morris, S. Paulauskis, J. Burnett, K. Shelton, T. Signoretti, S. Kaelin, W. Choueiri, T. Atkins, M. Penny, R. Burnett, K. Mallery, D. Curley, E. Tickoo, S. Reuter, V. Rathmell, W. Thorne, L. Boice, L. Huang, M. Fisher, J. Linehan, W. Vocke, C. Peterson, J. Worrell, R. Merino, M. Schmidt, L. Tamboli, P. Czerniak, B. Aldape, K. Wood, C. Boyd, J. Weaver, J. Iacocca, M. 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. Bshara, W. Gaudioso, C. Morrison, C. Dhir, R. Maranchie, J. Nelson, J. Parwani, A. Potapova, O. Fedosenko, K. Cheville, J. Thompson, R. Signoretti, S. Kaelin, W. Atkins, M. Tickoo, S. Reuter, V. Linehan, W. Vocke, C. Peterson, J. Merino, M. Schmidt, L. Tamboli, P. Mosquera, J. Rubin, M. Blute, M. 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. Davidsen, T. Wang, Z. Yang, L. Tarnuzzer, R. Zhang, J. Eley, G. Ferguson, M. Shaw, K. Guyer, M. Ozenberger, B. Sofia, H.
author_sort	Creighton, C.
building	Curtin Institutional Repository
collection	Online Access
description	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. Â© 2013 Macmillan Publishers Limited. All rights reserved.
first_indexed	2025-11-14T10:29:58Z
format	Journal Article
id	curtin-20.500.11937-66477
institution	Curtin University Malaysia
institution_category	Local University
last_indexed	2025-11-14T10:29:58Z
publishDate	2013
publisher	Nature Publishing Group
recordtype	eprints
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spelling	curtin-20.500.11937-664772018-04-30T02:48:32Z Comprehensivemolecular characterization of clear cell renal cell carcinoma Creighton, C. Morgan, M. Gunaratne, P. Wheeler, D. Gibbs, R. Robertson, A. Chu, A. Beroukhim, R. Cibulskis, K. Signoretti, S. Vandin, F. Wu, H. Raphael, B. Verhaak, R. Tamboli, P. Torres-Garcia, W. Akbani, R. Weinstein, J. Reuter, V. Hsieh, J. Brannon, A. Hakimi, A. Jacobsen, A. Ciriello, G. Reva, B. Ricketts, C. Linehan, W. Stuart, J. Rathmell, W. Shen, H. Laird, P. Muzny, D. Davis, C. Morgan, M. Xi, L. Chang, K. Kakkar, N. Trevino, L. Benton, S. Reid, J. Morton, D. Doddapaneni, H. Han, Y. Lewis, L. Dinh, H. Kovar, C. Zhu, Y. Santibanez, J. Wang, M. Hale, W. Kalra, D. Creighton, C. Wheeler, D. Gibbs, R. Getz, G. Cibulskis, K. Lawrence, M. Sougnez, C. Carter, S. Sivachenko, A. Lichtenstein, L. Stewart, C. Voet, D. Fisher, S. Gabriel, S. Lander, E. Beroukhim, R. Schumacher, S. Tabak, B. Saksena, G. Onofrio, R. Carter, S. Cherniack, A. Gentry, J. Ardlie, K. Sougnez, C. Getz, G. Gabriel, S. Meyerson, M. Robertson, A. Chu, A. Chun, H. Mungall, A. Sipahimalani, P. Stoll, D. Ally, A. Balasundaram, M. Butterfield, Y. Carlsen, R. Carter, C. Chuah, E. Coope, R. Dhalla, N. Gorski, S. Guin, R. Hirst, C. Hirst, M. Holt, R. Lebovitz, C. Lee, D. Li, H. Mayo, M. Moore, R. Pleasance, E. Plettner, P. Schein, J. Shafiei, A. Slobodan, J. Tam, A. Thiessen, N. Varhol, Richard Wye, N. Zhao, Y. Birol, I. Jones, S. Marra, M. Auman, J. Tan, D. Jones, C. Hoadley, K. Mieczkowski, P. Mose, L. Jefferys, S. Topal, M. Liquori, C. Turman, Y. Shi, Y. Waring, S. Buda, E. Walsh, J. Wu, J. Bodenheimer, T. Hoyle, A. Simons, J. Soloway, M. Balu, S. Parker, J. Hayes, D. Perou, C. Kucherlapati, R. Park, P. Shen, H. Triche, T. Weisenberger, D. Lai, P. Bootwalla, M. Maglinte, D. Mahurkar, S. Berman, B. Van den Berg, D. Cope, L. Baylin, S. Laird, P. Creighton, C. Wheeler, D. Getz, G. Noble, M. DiCara, D. Zhang, H. Cho, J. Heiman, D. Gehlenborg, N. Voet, D. Mallard, W. Lin, P. Frazer, S. Stojanov, P. Liu, Y. Zhou, L. Kim, J. Lawrence, M. Chin, L. Vandin, F. Wu, H. Raphael, B. Benz, C. Yau, C. Reynolds, S. Shmulevich, I. Verhaak, R. Torres-Garcia, W. Vegesna, R. Kim, H. Zhang, W. Cogdell, D. Jonasch, E. Ding, Z. Lu, Y. Akbani, R. Zhang, N. Unruh, A. Casasent, T. Wakefield, C. Tsavachidou, D. Chin, L. Mills, G. Weinstein, J. Jacobsen, A. Brannon, A. Ciriello, G. Schultz, N. Hakimi, A. Reva, B. Antipin, Y. Gao, J. Cerami, E. Gross, B. Aksoy, B. Sinha, R. Weinhold, N. Sumer, S. Taylor, B. Shen, R. Ostrovnaya, I. Hsieh, J. Berger, M. Ladanyi, M. Sander, C. Fei, S. Stout, A. Spellman, P. Rubin, D. Liu, T. Stuart, J. Sam, N. Paull, E. Carlin, D. Goldstein, T. Waltman, P. Ellrott, K. Zhu, J. Haussler, D. Gunaratne, P. Xiao, W. Shelton, C. Gardner, J. Penny, R. Sherman, M. Mallery, D. Morris, S. Paulauskis, J. Burnett, K. Shelton, T. Signoretti, S. Kaelin, W. Choueiri, T. Atkins, M. Penny, R. Burnett, K. Mallery, D. Curley, E. Tickoo, S. Reuter, V. Rathmell, W. Thorne, L. Boice, L. Huang, M. Fisher, J. Linehan, W. Vocke, C. Peterson, J. Worrell, R. Merino, M. Schmidt, L. Tamboli, P. Czerniak, B. Aldape, K. Wood, C. Boyd, J. Weaver, J. Iacocca, M. 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. Bshara, W. Gaudioso, C. Morrison, C. Dhir, R. Maranchie, J. Nelson, J. Parwani, A. Potapova, O. Fedosenko, K. Cheville, J. Thompson, R. Signoretti, S. Kaelin, W. Atkins, M. Tickoo, S. Reuter, V. Linehan, W. Vocke, C. Peterson, J. Merino, M. Schmidt, L. Tamboli, P. Mosquera, J. Rubin, M. Blute, M. 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. Davidsen, T. Wang, Z. Yang, L. Tarnuzzer, R. Zhang, J. Eley, G. Ferguson, M. Shaw, K. Guyer, M. Ozenberger, B. Sofia, H. 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. Â© 2013 Macmillan Publishers Limited. All rights reserved. 2013 Journal Article http://hdl.handle.net/20.500.11937/66477 10.1038/nature12222 Nature Publishing Group restricted
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title	Comprehensivemolecular characterization of clear cell renal cell carcinoma
title_full	Comprehensivemolecular characterization of clear cell renal cell carcinoma
title_fullStr	Comprehensivemolecular characterization of clear cell renal cell carcinoma
title_full_unstemmed	Comprehensivemolecular characterization of clear cell renal cell carcinoma
title_short	Comprehensivemolecular characterization of clear cell renal cell carcinoma
title_sort	comprehensivemolecular characterization of clear cell renal cell carcinoma
url	http://hdl.handle.net/20.500.11937/66477

Comprehensivemolecular characterization of clear cell renal cell carcinoma

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