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      Oncogenic signaling pathways in the Cancer Genome Atlas

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      Author(s)
      Sanchez-Vega, F.
      Mina, M.
      Armenia, J.
      Chatila, W. K.
      Luna, A.
      La, K. C.
      Dimitriadoy, S.
      Liu, D. L.
      Kantheti, H. S.
      Saghafinia, S.
      Chakravarty, D.
      Daian, F.
      Gao, Q.
      Bailey, M. H.
      Liang, W. -W.
      Foltz, S. M.
      Shmulevich, I.
      Ding, L.
      Heins, Z.
      Ochoa, A.
      Gross, B.
      Gao, J.
      Zhang, H.
      Kundra, R.
      Kandoth, C.
      Bahceci, I.
      Dervishi, L.
      Doğrusöz, Uğur
      Zhou, W.
      Shen, H.
      Laird, P. W.
      Way, G. P.
      Greene, C. S.
      Liang, H.
      Xiao, Y.
      Wang, C.
      Iavarone, A.
      Berger, A. H.
      Bivona, T. G.
      Lazar, A. J.
      Hammer, G. D.
      Giordano, T.
      Kwong, L. N.
      McArthur, G.
      Huang, C.
      Tward, A. D.
      Frederick, M. J.
      McCormick, F.
      Meyerson, M.
      Caesar-Johnson, S. J.
      Demchok, J. A.
      Felau, I.
      Kasapi, M.
      Ferguson, M. L.
      Hutter, C. M.
      Sofia, H. J.
      Tarnuzzer, R.
      Wang, Z.
      Yang, L.
      Zenklusen, J. C.
      Zhang, J. J.
      Chudamani, S.
      Liu, J.
      Lolla, L.
      Naresh, R.
      Pihl, T.
      Sun, Q.
      Wan, Y.
      Wu, Y.
      Cho, J.
      DeFreitas, T.
      Frazer, S.
      Gehlenborg, N.
      Getz, G.
      Heiman, D. I.
      Kim, J.
      Lawrence, M. S.
      Lin, P.
      Meier, S.
      Noble, M. S.
      Saksena, G.
      Voet, D.
      Zhang, H.
      Bernard, B.
      Chambwe, N.
      Dhankani, V.
      Knijnenburg, T.
      Kramer, R.
      Leinonen, K.
      Liu, Y.
      Miller, M.
      Reynolds, S.
      Shmulevich, I.
      Thorsson, V.
      Zhang, W.
      Akbani, R.
      Broom, B. M.
      Hegde, A. M.
      Ju, Z.
      Kanchi, R. S.
      Korkut, A.
      Li, J.
      Liang, H.
      Ling, S.
      Liu W.
      Lu, Y.
      Mills, G. B.
      Ng, K. -S.
      Rao, A.
      Ryan, M.
      Wang, J.
      Weinstein, J. N.
      Zhang, J.
      Abeshouse, A.
      Armenia, J.
      Chakravarty, D.
      Chatila, W. K.
      de, Bruijn, I.
      Gao, J.
      Gross, B. E.
      Heins, Z. J.
      Kundra, R.
      La, K.
      Ladanyi, M.
      Luna, A.
      Nissan, M. G.
      Ochoa, A.
      Phillips, S. M.
      Reznik, E.
      Sanchez-Vega, F.
      Sander, C.
      Schultz, N.
      Sheridan, R.
      Sumer, S. O.
      Sun, Y.
      Taylor, B. S.
      Wang, J.
      Zhang, H.
      Anur, P.
      Peto, M.
      Spellman, P.
      Benz, C.
      Stuart, J. M.
      Wong, C. K.
      Yau, C.
      Hayes, D. N.
      Parker, J. S.
      Wilkerson, M. D.
      Ally, A.
      Balasundaram, M.
      Bowlby, R.
      Brooks, D.
      Carlsen, R.
      Chuah, E.
      Dhalla, N.
      Holt, R.
      Jones, S. J. M.
      Kasaian, K.
      Lee, D.
      Ma, Y.
      Marra, M. A.
      Mayo, M.
      Moore, R. A.
      Mungall, A. J.
      Mungall, K.
      Robertson, A. G.
      Sadeghi, S.
      Schein, J. E.
      Sipahimalani, P.
      Tam, A.
      Thiessen, N.
      Tse, K.
      Wong, T.
      Berger, A. C.
      Beroukhim, R.
      Cherniack, A. D.
      Cibulskis, C.
      Gabriel, S. B.
      Gao, G. F.
      Ha, G.
      Meyerson, M.
      Schumacher, S. E.
      Shih, J.
      Kucherlapati, M. H.
      Kucherlapati, R. S.
      Baylin, S.
      Cope, L.
      Danilova, L.
      Bootwalla, M. S.
      Lai, P. H.
      Maglinte, D. T.
      Van, Den, Berg, D. J.
      Weisenberger, D. J.
      Auman, J. T.
      Balu, S.
      Bodenheimer, T.
      Fan, C.
      Hoadley, K. A.
      Hoyle, A. P.
      Jefferys, S. R.
      Jones, C. D.
      Meng, S.
      Mieczkowski, P. A.
      Mose, L. E.
      Perou, A. H.
      Perou, C. M.
      Roach, J.
      Shi, Y.
      Simons, J. V.
      Skelly, T.
      Soloway, M. G.
      Tan, D.
      Veluvolu, U.
      Fan, H.
      Hinoue, T.
      Laird, P. W.
      Shen, H.
      Zhou, W.
      Bellair, M.
      Chang, K.
      Covington, K.
      Creighton, C. J.
      Dinh, H.
      Doddapaneni, H.
      Donehower, L. A.
      Drummond, J.
      Gibbs, R. A.
      Glenn, R.
      Hale, W.
      Han, Y.
      Hu, J.
      Korchina, V.
      Lee, S.
      Lewis, L.
      Li, W.
      Liu, X.
      Morgan, M.
      Morton, D.
      Muzny, D.
      Santibanez, J.
      Sheth, M.
      Shinbrot, E.
      Wang, L.
      Wang, M.
      Wheeler, D. A.
      Xi, L.
      Zhao, F.
      Hess, J.
      Appelbaum, E. L.
      Bailey, M.
      Cordes, M. G.
      Ding, L.
      Fronick, C. C.
      Fulton, L. A.
      Fulton, R. S.
      Kandoth, C.
      Mardis, E. R.
      McLellan, M. D.
      Miller, C. A.
      Schmidt, H. K.
      Wilson, R. K.
      Crain, D.
      Curley, E.
      Gardner, J.
      Lau, K.
      Mallery, D.
      Morris, S.
      Paulauskis, J.
      Penny, R.
      Shelton, C.
      Shelton, T.
      Sherman, M.
      Thompson, E.
      Yena, P.
      Bowen, J.
      Gastier-Foster, J. M.
      Gerken, M.
      Leraas, K. M.
      Lichtenberg, T. M.
      Ramirez, N. C.
      Wise, L.
      Zmuda, E.
      Corcoran, N.
      Costello, T.
      Hovens, C.
      Carvalho, A. L.
      de, Carvalho, A. C.
      Fregnani, J. H.
      Longatto-Filho, A.
      Reis, R. M.
      Scapulatempo-Neto, C.
      Silveira, H. C. S.
      Vidal, D. O.
      Burnette, A.
      Eschbacher, J.
      Hermes, B.
      Noss, A.
      Singh, R.
      Anderson, M. L.
      Castro, P. D.
      Ittmann, M.
      Huntsman, D.
      Kohl, B.
      Le, X.
      Thorp, R.
      Andry, C.
      Duffy, E. R.
      Lyadov, V.
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      Tavobilov, M.
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      Muto, M.
      Raut, C. P.
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      Devine, K.
      Fulop, J.
      Ostrom, Q. T.
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      Wolinsky, Y.
      Sloan, A. E.
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      Quintero-Aguilo, M.
      Carlotti, C. G.
      Jr.
      Dos, Santos, J. S.
      Kemp, R.
      Sankarankuty, A.
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      Bowman, R.
      Fong, K. M.
      Yang, I.
      Korst, R.
      Rathmell, W. K.
      Fantacone-Campbell, J. L.
      Hooke, J. A.
      Kovatich, A. J.
      Shriver, C. D.
      DiPersio, J.
      Drake, B.
      Govindan, R.
      Heath, S.
      Ley, T.
      Van, Tine, B.
      Westervelt, P.
      Rubin, M. A.
      Lee, J. I.
      Aredes, N. D.
      Mariamidze, A.
      Van, Allen, E. M.
      Cherniack, A. D.
      Ciriello, G.
      Sander, C.
      Schultz, N.
      The, Cancer, Genome, Atlas, Research, Network.tif
      Date
      2018
      Source Title
      Cell
      Print ISSN
      0092-8674
      Electronic ISSN
      1875-9777
      Publisher
      Cell Press
      Volume
      173
      Issue
      2
      Pages
      321 - 337
      Language
      English
      Type
      Article
      Item Usage Stats
      349
      views
      1,218
      downloads
      Abstract
      Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies.
      Keywords
      Cancer genome atlas
      Cancer genomics
      Combination therapy
      Pan-cancer
      PanCanAtlas
      Precision oncology
      Signaling pathways
      TCGA
      Therapeutics
      Whole exome sequencing
      Permalink
      http://hdl.handle.net/11693/49844
      Published Version (Please cite this version)
      https://doi.org/10.1016/j.cell.2018.03.035
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      • Department of Computer Engineering 1561
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        Chang, C.; Zhang, C.; Zhang, Q.; Sahin, O.; Wang, H.; Xu, J.; Xiao, Y.; Zhang, J.; Rehman, S. K.; Li, P.; Hung, M. C.; Behbod, F.; Yu, D. (Impact Journals LLC, 2016-05)
        Metabolic reprogramming is a hallmark of cancer. Elevated glycolysis in cancer cells switches the cellular metabolic flux to produce more biological building blocks, thereby sustaining rapid proliferation. Recently, new ...
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        Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells 

        Küçük, C.; Jiang, B.; Hu X.; Zhang W.; Chan J.K.C.; Xiao W.; Lack, N.; Alkan, C.; Williams J.C.; Avery, K.N.; Kavak P.; Scuto, A.; Sen, E.; Gaulard P.; Staudt L.; Iqbal J.; Zhang W.; Cornish, A.; Gong Q.; Yang Q.; Sun H.; D'Amore F.; Leppä, S.; Liu W.; Fu, K.; De Leval L.; McKeithan, T.; Chan W.C. (Nature Publishing Group, 2015)
        Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell ...

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