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Comprehensive molecular characterization of the hippo signaling pathway in cancer

Title: Comprehensive molecular characterization of the hippo signaling pathway in cancer
Authors: Wang, Y; Xu, X; Maglic, D; Dill, MT; Mojumdar, K; Ng, PK-S; Jeong, KJ; Tsang, YH; Moreno, D; Bhavana, VH; Peng, X; Ge, Z; Chen, H; Li, J; Chen, Z; Zhang, H; Han, L; Du, D; Creighton, CJ; Mills, GB; Camargo, F; Liang, H; Caesar-Johnson, SJ; Demchok, JA; Felau, I; Kasapi, M; Ferguson, ML; Hutter, CM; Sofia, HJ; Tarnuzzer, R; Wang, Z; Yang, L; Zenklusen, JC; Zhang, JJ; 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, DI; Kim, J; Lawrence, MS; Lin, P; Meier, S; Noble, MS; Saksena, G; Voet, D; 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, BM; Hegde, AM; Ju, Z; Kanchi, RS; Korkut, A; Ling, S; Liu, W; Lu, Y; Ng, K-S; Rao, A; Ryan, M; Wang, J; Weinstein, JN; Zhang, J; Abeshouse, A; Armenia, J; Chakravarty, D; Chatila, WK; de Bruijn, I; Gao, J; Gross, BE; Heins, ZJ; Kundra, R; La, K; Ladanyi, M; Luna, A; Nissan, MG; Ochoa, A; Phillips, SM; Reznik, E; Sanchez-Vega, F; Sander, C; Schultz, N; Sheridan, R; Sumer, SO; Sun, Y; Taylor, BS; Anur, P; Peto, M; Spellman, P; Benz, C; Stuart, JM; Wong, CK; Yau, C; Hayes, DN; Parker, JS; Wilkerson, MD; Ally, A; Balasundaram, M; Bowlby, R; Brooks, D; Carlsen, R; Chuah, E; Dhalla, N; Holt, R; Jones, SJM; Kasaian, K; Lee, D; Ma, Y; Marra, MA; Mayo, M; Moore, RA; Mungall, AJ; Mungall, K; Robertson, AG; Sadeghi, S; Schein, JE; Sipahimalani, P; Tam, A; Thiessen, N; Tse, K; Wong, T; Berger, AC; Beroukhim, R; Cherniack, AD; Cibulskis, C; Gabriel, SB; Gao, GF; Ha, G; Meyerson, M; Schumacher, SE; Shih, J; Kucherlapati, MH; Kucherlapati, RS; Baylin, S; Cope, L; Danilova, L; Bootwalla, MS; Lai, PH; Maglinte, DT; Van Den Berg, DJ; Weisenberger, DJ; Auman, JT; Balu, S; Bodenheimer, T; Fan, C; Hoadley, KA; Hoyle, AP; Jefferys, SR; Jones, CD; Meng, S; Mieczkowski, PA; Mose, LE; Perou, AH; Perou, CM; Roach, J; Shi, Y; Simons, JV; Skelly, T; Soloway, MG; Tan, D; Veluvolu, U; Fan, H; Hinoue, T; Laird, PW; Shen, H; Zhou, W; Bellair, M; Chang, K; Covington, K; Dinh, H; Doddapaneni, H; Donehower, LA; Drummond, J; Gibbs, RA; 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, DA; Xi, L; Zhao, F; Hess, J; Appelbaum, EL; Bailey, M; Cordes, MG; Ding, L; Fronick, CC; Fulton, LA; Fulton, RS; Kandoth, C; Mardis, ER; McLellan, MD; Miller, CA; Schmidt, HK; Wilson, RK; 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, JM; Gerken, M; Leraas, KM; Lichtenberg, TM; Ramirez, NC; Wise, L; Zmuda, E; Corcoran, N; Costello, T; Hovens, C; Carvalho, AL; de Carvalho, AC; Fregnani, JH; Longatto-Filho, A; Reis, RM; Scapulatempo-Neto, C; Silveira, HCS; Vidal, DO; Burnette, A; Eschbacher, J; Hermes, B; Noss, A; Singh, R; Anderson, ML; Castro, PD; Ittmann, M; Huntsman, D; Kohl, B; Le, X; Thorp, R; Andry, C; Duffy, ER; Lyadov, V; Paklina, O; Setdikova, G; Shabunin, A; Tavobilov, M; McPherson, C; Warnick, R; Berkowitz, R; Cramer, D; Feltmate, C; Horowitz, N; Kibel, A; Muto, M; Raut, CP; Malykh, A; Barnholtz-Sloan, JS; Barrett, W; Devine, K; Fulop, J; Ostrom, QT; Shimmel, K; Wolinsky, Y; Sloan, AE; De Rose, A; Giuliante, F; Goodman, M; Karlan, BY; Hagedorn, CH; Eckman, J; Harr, J; Myers, J; Tucker, K; Zach, LA; Deyarmin, B; Hu, H; Kvecher, L; Larson, C; Mural, RJ; Somiari, S; Vicha, A; Zelinka, T; Bennett, J; Iacocca, M; Rabeno, B; Swanson, P; Latour, M; Lacombe, L; Têtu, B; Bergeron, A; McGraw, M; Staugaitis, SM; Chabot, J; Hibshoosh, H; Sepulveda, A; Su, T; Wang, T; Potapova, O; Voronina, O; Desjardins, L; Mariani, O; Roman-Roman, S; Sastre, X; Stern, M-H; Cheng, F; Signoretti, S; Berchuck, A; Bigner, D; Lipp, E; Marks, J; McCall, S; McLendon, R; Secord, A; Sharp, A; Behera, M; Brat, DJ; Chen, A; Delman, K; Force, S; Khuri, F; Magliocca, K; Maithel, S; Olson, JJ; Owonikoko, T; Pickens, A; Ramalingam, S; Shin, DM; Sica, G; Van Meir, EG; Eijckenboom, W; Gillis, A; Korpershoek, E; Looijenga, L; Oosterhuis, W; Stoop, H; van Kessel, KE; Zwarthoff, EC; Calatozzolo, C; Cuppini, L; Cuzzubbo, S; DiMeco, F; Finocchiaro, G; Mattei, L; Perin, A; Pollo, B; Chen, C; Houck, J; Lohavanichbutr, P; Hartmann, A; Stoehr, C; Stoehr, R; Taubert, H; Wach, S; Wullich, B; Kycler, W; Murawa, D; Wiznerowicz, M; Chung, K; Edenfield, WJ; Martin, J; Baudin, E; Bubley, G; Bueno, R; De Rienzo, A; Richards, WG; Kalkanis, S; Mikkelsen, T; Noushmehr, H; Scarpace, L; Girard, N; Aymerich, M; Campo, E; Giné, E; Guillermo, AL; Van Bang, N; Hanh, PT; Phu, BD; Tang, Y; Colman, H; Evason, K; Dottino, PR; Martignetti, JA; Gabra, H; Juhl, H; Akeredolu, T; Stepa, S; Hoon, D; Ahn, K; Kang, KJ; Beuschlein, F; Breggia, A; Birrer, M; Bell, D; Borad, M; Bryce, AH; Castle, E; Chandan, V; Cheville, J; Copland, JA; Farnell, M; Flotte, T; Giama, N; Ho, T; Kendrick, M; Kocher, J-P; Kopp, K; Moser, C; Nagorney, D; O’Brien, D; O’Neill, BP; Patel, T; Petersen, G; Que, F; Rivera, M; Roberts, L; Smallridge, R; Smyrk, T; Stanton, M; Thompson, RH; Torbenson, M; Yang, JD; Zhang, L; Brimo, F; Ajani, JA; Gonzalez, AMA; Behrens, C; Bondaruk, J; Broaddus, R; Czerniak, B; Esmaeli, B; Fujimoto, J; Gershenwald, J; Guo, C; Lazar, AJ; Logothetis, C; Meric-Bernstam, F; Moran, C; Ramondetta, L; Rice, D; Sood, A; Tamboli, P; Thompson, T; Troncoso, P; Tsao, A; Wistuba, I; Carter, C; Haydu, L; Hersey, P; Jakrot, V; Kakavand, H; Kefford, R; Lee, K; Long, G; Mann, G; Quinn, M; Saw, R; Scolyer, R; Shannon, K; Spillane, A; Stretch, J; Synott, M; Thompson, J; Wilmott, J; Al-Ahmadie, H; Chan, TA; Ghossein, R; Gopalan, A; Levine, DA; Reuter, V; Singer, S; Singh, B; Tien, NV; Broudy, T; Mirsaidi, C; Nair, P; Drwiega, P; Miller, J; Smith, J; Zaren, H; Park, J-W; Hung, NP; Kebebew, E; Linehan, WM; Metwalli, AR; Pacak, K; Pinto, PA; Schiffman, M; Schmidt, LS; Vocke, CD; Wentzensen, N; Worrell, R; Yang, H; Moncrieff, M; Goparaju, C; Melamed, J; Pass, H; Botnariuc, N; Caraman, I; Cernat, M; Chemencedji, I; Clipca, A; Doruc, S; Gorincioi, G; Mura, S; Pirtac, M; Stancul, I; Tcaciuc, D; Albert, M; Alexopoulou, I; Arnaout, A; Bartlett, J; Engel, J; Gilbert, S; Parfitt, J; Sekhon, H; Thomas, G; Rassl, DM; Rintoul, RC; Bifulco, C; Tamakawa, R; Urba, W; Hayward, N; Timmers, H; Antenucci, A; Facciolo, F; Grazi, G; Marino, M; Merola, R; de Krijger, R; Gimenez-Roqueplo, A-P; Piché, A; Chevalier, S; McKercher, G; Birsoy, K; Barnett, G; Brewer, C; Farver, C; Naska, T; Pennell, NA; Raymond, D; Schilero, C; Smolenski, K; Williams, F; Morrison, C; Borgia, JA; Liptay, MJ; Pool, M; Seder, CW; Junker, K; Omberg, L; Dinkin, M; Manikhas, G; Alvaro, D; Bragazzi, MC; Cardinale, V; Carpino, G; Gaudio, E; Chesla, D; Cottingham, S; Dubina, M; Moiseenko, F; Dhanasekaran, R; Becker, K-F; Janssen, K-P; Slotta-Huspenina, J; Abdel-Rahman, MH; Aziz, D; Bell, S; Cebulla, CM; Davis, A; Duell, R; Elder, JB; Hilty, J; Kumar, B; Lang, J; Lehman, NL; Mandt, R; Nguyen, P; Pilarski, R; Rai, K; Schoenfield, L; Senecal, K; Wakely, P; Hansen, P; Lechan, R; Powers, J; Tischler, A; Grizzle, WE; Sexton, KC; Kastl, A; Henderson, J; Porten, S; Waldmann, J; Fassnacht, M; Asa, SL; Schadendorf, D; Couce, M; Graefen, M; Huland, H; Sauter, G; Schlomm, T; Simon, R; Tennstedt, P; Olabode, O; Nelson, M; Bathe, O; Carroll, PR; Chan, JM; Disaia, P; Glenn, P; Kelley, RK; Landen, CN; Phillips, J; Prados, M; Simko, J; Smith-McCune, K; VandenBerg, S; Roggin, K; Fehrenbach, A; Kendler, A; Sifri, S; Steele, R; Jimeno, A; Carey, F; Forgie, I; Mannelli, M; Carney, M; Hernandez, B; Campos, B; Herold-Mende, C; Jungk, C; Unterberg, A; von Deimling, A; Bossler, A; Galbraith, J; Jacobus, L; Knudson, M; Knutson, T; Ma, D; Milhem, M; Sigmund, R; Godwin, AK; Madan, R; Rosenthal, HG; Adebamowo, C; Adebamowo, SN; Boussioutas, A; Beer, D; Giordano, T; Mes-Masson, A-M; Saad, F; Bocklage, T; Landrum, L; Mannel, R; Moore, K; Moxley, K; Postier, R; Walker, J; Zuna, R; Feldman, M; Valdivieso, F; Dhir, R; Luketich, J; Pinero, EMM; Quintero-Aguilo, M; Carlotti, CG; Dos Santos, JS; Kemp, R; Sankarankuty, A; Tirapelli, D; Catto, J; Agnew, K; Swisher, E; Creaney, J; Robinson, B; Shelley, CS; Godwin, EM; Kendall, S; Shipman, C; Bradford, C; Carey, T; Haddad, A; Moyer, J; Peterson, L; Prince, M; Rozek, L; Wolf, G; Bowman, R; Fong, KM; Yang, I; Korst, R; Rathmell, WK; Fantacone-Campbell, JL; Hooke, JA; Kovatich, AJ; Shriver, CD; DiPersio, J; Drake, B; Govindan, R; Heath, S; Ley, T; Van Tine, B; Westervelt, P; Rubin, MA; Lee, JI; Aredes, ND; Mariamidze, A
Publisher Information: Elsevier
Publication Year: 2018
Collection: White Rose Research Online (Universities of Leeds, Sheffield & York)
Description: Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era.
Document Type: article in journal/newspaper
File Description: text
Language: English
ISSN: 2211-1247
Relation: https://eprints.whiterose.ac.uk/id/eprint/142514/8/1-s2.0-S221112471831564X-main.pdf; Wang, Y, Xu, X, Maglic, D et al. (744 more authors) (2018) Comprehensive molecular characterization of the hippo signaling pathway in cancer. Cell Reports, 25 (5). 1304-1317.e5. ISSN: 2211-1247
Availability: https://eprints.whiterose.ac.uk/id/eprint/142514/
Rights: cc_by_nc_nd_4
Accession Number: edsbas.6356CB14
Database: BASE