Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Liu, Y.; Sethi, N.S.; Hinoue, T.; Schneider, B.G.; Cherniack, A.D.; Sanchez-Vega, F.; Seoane, J.A.; Farshidfar, F.; Bowlby, R.; Islam, M.; Kim, J.; Chatila, W.; Akbani, R.; Kanchi, R.S.; Rabkin, C.S.; Willis, J.E.; Wang, K.K.; Mccall, S.J.; Mishra, L.; Ojesina, A.I.; Bullman, S.; Pedamallu, C.S.; Lazar, A.J.; Sakai, R.; Thorsson, V.; Bass, A.J.; Laird, P.W.; 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.(.; Chudamani, S.; Liu, J.; Lolla, L.; Naresh, R.; Pihl, T.; Sun, Q.; Wan, Y.; Ye, W.; 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.; Zhenlin, J.; Kanchi, R.S.; Korkut, A.; Jun, L.; Liang, H.; Ling, S.; Liu, W.; Yiling, L.; Mills, G.B.; Kwok-Shing, N.; Rao, A.; Ryan, M.; Wang, J.; Weinstein, J.N.; Zhang, J.; Abeshouse, A.; Armenia, J.; Chakravarty, D.; Chatila, W.K.; Bruijn, I.; Gao, J.; Gross, B.E.; Heins, Z.J.; Kundra, R.; Konnor, L.; 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.; Yussanne, M.; 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.; Gavin, H.; 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.; Jianhong, H.; Korchina, V.; Lee, S.; Lewis, L.; Wei, L.; Liu, X.; Morgan, M.; Morton, D.; Muzny, D.; Santibanez, J.; Sheth, M.; Shinbrot, E.; Wang, L.; Wang, M.; Wheeler, D.A.; Liu, X.; 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.; Xuan, L.; Thorp, R.; Andry, C.; Duffy, E.R.; 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, C.P.; Malykh, A.; Barnholtz-Sloan, J.S.; Barrett, W.; Devine, K.; Fulop, J.; Ostrom, Q.T.; Shimmel, K.; Wolinsky, Y.; Sloan, A.E.; De Rose, A.; Giuliante, F.; Goodman, M.; Karlan, B.Y.; Hagedorn, C.H.; Eckman, J.; Harr, J.; Myers, J.; Tucker, K.; Zach, L.A.; Deyarmin, B.; Hai, H.; Kvecher, L.; Larson, C.; Mural, R.J.; 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, S.M.; Chabot, J.; Hibshoosh, H.; Sepulveda, A.; Tao, S.; Wang, T.; Potapova, O.; Voronina, O.; Desjardins, L.; Mariani, O.; Roman-Roman, S.; Sastre, X.; Stern, M.; Cheng, F.; Signoretti, S.; Berchuck, A.; Bigner, D.; Lipp, E.; Marks, J.; Mccall, S.; Mclendon, R.; Secord, A.; Sharp, A.; Behera, M.; Brat, D.J.; Chen, A.; Delman, K.; Force, S.; Khuri, F.; Magliocca, K.; Maithel, S.; Olson, J.J.; Owonikoko, T.; Pickens, A.; Ramalingam, S.; Shin, D.M.; Sica, G.; Van Meir, E.G.; Zhang, H.; Eijckenboom, W.; Gillis, A.; Korpershoek, E.; Looijenga, L.; Oosterhuis, W.; Stoop, H.; van Kessel, K.E.; Zwarthoff, E.C.; 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, W.J.; Martin, J.; Baudin, E.; Bubley, G.; Bueno, R.; De Rienzo, A.; Richards, W.G.; Kalkanis, S.; Mikkelsen, T.; Noushmehr, H.; Scarpace, L.; Girard, N.; Aymerich, M.; Campo, E.; Giné, E.; Guillermo, A.L.; Van Bang, N.; Hanh, P.T.; Phu, B.D.; Tang, Y.; Colman, H.; Evason, K.; Dottino, P.R.; Martignetti, J.A.; Gabra, H.; Juhl, H.; Akeredolu, T.; Stepa, S.; Hoon, D.; Ahn, K.; Kang, K.J.; Beuschlein, F.; Breggia, A.; Birrer, M.; Bell, D.; Borad, M.; Bryce, A.H.; Castle, E.; Chandan, V.; Cheville, J.; Copland, J.A.; Farnell, M.; Flotte, T.; Giama, N.; Thai, H.; Kendrick, M.; Kocher, J.; Kopp, K.; Moser, C.; Nagorney, D.; O’Brien, D.; O’Neill, B.P.; Patel, T.; Petersen, G.; Que, F.; Rivera, M.; Roberts, L.; Smallridge, R.; Smyrk, T.; Stanton, M.; Thompson, R.H.; Torbenson, M.; Yang, J.D.; Zhang, L.; Brimo, F.; Ajani, J.A.; Gonzalez, A.M.A.; Behrens, C.; Bondaruk, J.; Broaddus, R.; Czerniak, B.; Esmaeli, B.; Fujimoto, J.; Gershenwald, J.; Guo, C.; Lazar, A.J.; 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, T.A.; Ghossein, R.; Gopalan, A.; Levine, D.A.; Reuter, V.; Singer, S.; Singh, B.; Tien, N.V.; Broudy, T.; Mirsaidi, C.; Nair, P.; Drwiega, P.; Miller, J.; Smith, J.; Zaren, H.; Park, J.; Hung, N.P.; Kebebew, E.; Linehan, W.M.; Metwalli, A.R.; Pacak, K.; Pinto, P.A.; Schiffman, M.; Schmidt, L.S.; Vocke, C.D.; 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, D.M.; Rintoul, R.C.; 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.; Piché, A.; Chevalier, S.; Mckercher, G.; Birsoy, K.; Barnett, G.; Brewer, C.; Farver, C.; Naska, T.; Pennell, N.A.; Raymond, D.; Schilero, C.; Smolenski, K.; Williams, F.; Morrison, C.; Borgia, J.A.; Liptay, M.J.; Pool, M.; Seder, C.W.; Junker, K.; Omberg, L.; Dinkin, M.; Manikhas, G.; Alvaro, D.; Bragazzi, M.C.; Cardinale, V.; Carpino, G.; Gaudio, E.; Chesla, D.; Cottingham, S.; Dubina, M.; Moiseenko, F.; Dhanasekaran, R.; Becker, K.; Janssen, K.; Slotta-Huspenina, J.; Abdel-Rahman, M.H.; Aziz, D.; Bell, S.; Cebulla, C.M.; Davis, A.; Duell, R.; Elder, J.B.; Hilty, J.; Kumar, B.; Lang, J.; Lehman, N.L.; Mandt, R.; Nguyen, P.; Pilarski, R.; Rai, K.; Schoenfield, L.; Senecal, K.; Wakely, P.; Hansen, P.; Lechan, R.; Powers, J.; Tischler, A.; Grizzle, W.E.; Sexton, K.C.; Kastl, A.; Henderson, J.; Porten, S.; Waldmann, J.; Fassnacht, M.; Asa, S.L.; Schadendorf, D.; Couce, M.; Graefen, M.; Huland, H.; Sauter, G.; Schlomm, T.; Simon, R.; Tennstedt, P.; Olabode, O.; Nelson, M.; Bathe, O.; Carroll, P.R.; Chan, J.M.; Disaia, P.; Glenn, P.; Kelley, R.K.; Landen, C.N.; 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.; Deqin, M.; Milhem, M.; Sigmund, R.; Godwin, A.K.; Madan, R.; Rosenthal, H.G.; Adebamowo, C.; Adebamowo, S.N.; Boussioutas, A.; Beer, D.; Giordano, T.; Mes-Masson, A.; 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, E.M.M.; Quintero-Aguilo, M.; Carlotti, C.G.; Dos Santos, J.S.; Kemp, R.; Sankarankuty, A.; Tirapelli, D.; Catto, J.; Agnew, K.; Swisher, E.; Creaney, J.; Robinson, B.; Shelley, C.S.; Godwin, E.M.; Kendall, S.; Shipman, C.; Bradford, C.; Carey, T.; Haddad, A.; Moyer, J.; Peterson, L.; Prince, M.; Rozek, L.; Wolf, G.; 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.

doi:10.1016/j.ccell.2018.03.010

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1.

Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas / Y. Liu, N.S. Sethi, T. Hinoue, B.G. Schneider, A.D. Cherniack, F. Sanchez-Vega, J.A. Seoane, F. Farshidfar, R. Bowlby, M. Islam, J. Kim, W. Chatila, R. Akbani, R.S. Kanchi, C.S. Rabkin, J.E. Willis, K.K. Wang, S.J. Mccall, L. Mishra, A.I. Ojesina, S. Bullman, C.S. Pedamallu, A.J. Lazar, R. Sakai, V. Thorsson, A.J. Bass, P.W. Laird, S.J. Caesar-Johnson, J.A. Demchok, I. Felau, M. Kasapi, M.L. Ferguson, C.M. Hutter, H.J. Sofia, R. Tarnuzzer, Z. Wang, L. Yang, J.C. Zenklusen, J.(. Zhang, S. Chudamani, J. Liu, L. Lolla, R. Naresh, T. Pihl, Q. Sun, Y. Wan, W. Ye, J. Cho, T. Defreitas, S. Frazer, N. Gehlenborg, G. Getz, D.I. Heiman, J. Kim, M.S. Lawrence, P. Lin, S. Meier, M.S. Noble, G. Saksena, D. Voet, H. Zhang, B. Bernard, N. Chambwe, V. Dhankani, T. Knijnenburg, R. Kramer, K. Leinonen, Y. Liu, M. Miller, S. Reynolds, I. Shmulevich, V. Thorsson, W. Zhang, R. Akbani, B.M. Broom, A.M. Hegde, J. Zhenlin, R.S. Kanchi, A. Korkut, L. Jun, H. Liang, S. Ling, W. Liu, L. Yiling, G.B. Mills, N. Kwok-Shing, A. Rao, M. Ryan, J. Wang, J.N. Weinstein, J. Zhang, A. Abeshouse, J. Armenia, D. Chakravarty, W.K. Chatila, I. Bruijn, J. Gao, B.E. Gross, Z.J. Heins, R. Kundra, L. Konnor, M. Ladanyi, A. Luna, M.G. Nissan, A. Ochoa, S.M. Phillips, E. Reznik, F. Sanchez-Vega, C. Sander, N. Schultz, R. Sheridan, S.O. Sumer, Y. Sun, B.S. Taylor, J. Wang, H. Zhang, P. Anur, M. Peto, P. Spellman, C. Benz, J.M. Stuart, C.K. Wong, C. Yau, D.N. Hayes, J.S. Parker, M.D. Wilkerson, A. Ally, M. Balasundaram, R. Bowlby, D. Brooks, R. Carlsen, E. Chuah, N. Dhalla, R. Holt, S.J.M. Jones, K. Kasaian, D. Lee, M. Yussanne, M.A. Marra, M. Mayo, R.A. Moore, A.J. Mungall, K. Mungall, A.G. Robertson, S. Sadeghi, J.E. Schein, P. Sipahimalani, A. Tam, N. Thiessen, K. Tse, T. Wong, A.C. Berger, R. Beroukhim, A.D. Cherniack, C. Cibulskis, S.B. Gabriel, G.F. Gao, H. Gavin, M. Meyerson, S.E. Schumacher, J. Shih, M.H. Kucherlapati, R.S. Kucherlapati, S. Baylin, L. Cope, L. Danilova, M.S. Bootwalla, P.H. Lai, D.T. Maglinte, D.J. Van Den Berg, D.J. Weisenberger, J.T. Auman, S. Balu, T. Bodenheimer, C. Fan, K.A. Hoadley, A.P. Hoyle, S.R. Jefferys, C.D. Jones, S. Meng, P.A. Mieczkowski, L.E. Mose, A.H. Perou, C.M. Perou, J. Roach, Y. Shi, J.V. Simons, T. Skelly, M.G. Soloway, D. Tan, U. Veluvolu, H. Fan, T. Hinoue, P.W. Laird, H. Shen, W. Zhou, M. Bellair, K. Chang, K. Covington, C.J. Creighton, H. Dinh, H. Doddapaneni, L.A. Donehower, J. Drummond, R.A. Gibbs, R. Glenn, W. Hale, Y. Han, H. Jianhong, V. Korchina, S. Lee, L. Lewis, L. Wei, X. Liu, M. Morgan, D. Morton, D. Muzny, J. Santibanez, M. Sheth, E. Shinbrot, L. Wang, M. Wang, D.A. Wheeler, X. Liu, F. Zhao, J. Hess, E.L. Appelbaum, M. Bailey, M.G. Cordes, L. Ding, C.C. Fronick, L.A. Fulton, R.S. Fulton, C. Kandoth, E.R. Mardis, M.D. Mclellan, C.A. Miller, H.K. Schmidt, R.K. Wilson, D. Crain, E. Curley, J. Gardner, K. Lau, D. Mallery, S. Morris, J. Paulauskis, R. Penny, C. Shelton, T. Shelton, M. Sherman, E. Thompson, P. Yena, J. Bowen, J.M. Gastier-Foster, M. Gerken, K.M. Leraas, T.M. Lichtenberg, N.C. Ramirez, L. Wise, E. Zmuda, N. Corcoran, T. Costello, C. Hovens, A.L. Carvalho, A.C. de Carvalho, J.H. Fregnani, A. Longatto-Filho, R.M. Reis, C. Scapulatempo-Neto, H.C.S. Silveira, D.O. Vidal, A. Burnette, J. Eschbacher, B. Hermes, A. Noss, R. Singh, M.L. Anderson, P.D. Castro, M. Ittmann, D. Huntsman, B. Kohl, L. Xuan, R. Thorp, C. Andry, E.R. Duffy, V. Lyadov, O. Paklina, G. Setdikova, A. Shabunin, M. Tavobilov, C. Mcpherson, R. Warnick, R. Berkowitz, D. Cramer, C. Feltmate, N. Horowitz, A. Kibel, M. Muto, C.P. Raut, A. Malykh, J.S. Barnholtz-Sloan, W. Barrett, K. Devine, J. Fulop, Q.T. Ostrom, K. Shimmel, Y. Wolinsky, A.E. Sloan, A. De Rose, F. Giuliante, M. Goodman, B.Y. Karlan, C.H. Hagedorn, J. Eckman, J. Harr, J. Myers, K. Tucker, L.A. Zach, B. Deyarmin, H. Hai, L. Kvecher, C. Larson, R.J. Mural, S. Somiari, A. Vicha, T. Zelinka, J. Bennett, M. Iacocca, B. Rabeno, P. Swanson, M. Latour, L. Lacombe, B. Têtu, A. Bergeron, M. Mcgraw, S.M. Staugaitis, J. Chabot, H. Hibshoosh, A. Sepulveda, S. Tao, T. Wang, O. Potapova, O. Voronina, L. Desjardins, O. Mariani, S. Roman-Roman, X. Sastre, M. Stern, F. Cheng, S. Signoretti, A. Berchuck, D. Bigner, E. Lipp, J. Marks, S. Mccall, R. Mclendon, A. Secord, A. Sharp, M. Behera, D.J. Brat, A. Chen, K. Delman, S. Force, F. Khuri, K. Magliocca, S. Maithel, J.J. Olson, T. Owonikoko, A. Pickens, S. Ramalingam, D.M. Shin, G. Sica, E.G. Van Meir, H. Zhang, W. Eijckenboom, A. Gillis, E. Korpershoek, L. Looijenga, W. Oosterhuis, H. Stoop, K.E. van Kessel, E.C. Zwarthoff, C. Calatozzolo, L. Cuppini, S. Cuzzubbo, F. Dimeco, G. Finocchiaro, L. Mattei, A. Perin, B. Pollo, C. Chen, J. Houck, P. Lohavanichbutr, A. Hartmann, C. Stoehr, R. Stoehr, H. Taubert, S. Wach, B. Wullich, W. Kycler, D. Murawa, M. Wiznerowicz, K. Chung, W.J. Edenfield, J. Martin, E. Baudin, G. Bubley, R. Bueno, A. De Rienzo, W.G. Richards, S. Kalkanis, T. Mikkelsen, H. Noushmehr, L. Scarpace, N. Girard, M. Aymerich, E. Campo, E. Giné, A.L. Guillermo, N. Van Bang, P.T. Hanh, B.D. Phu, Y. Tang, H. Colman, K. Evason, P.R. Dottino, J.A. Martignetti, H. Gabra, H. Juhl, T. Akeredolu, S. Stepa, D. Hoon, K. Ahn, K.J. Kang, F. Beuschlein, A. Breggia, M. Birrer, D. Bell, M. Borad, A.H. Bryce, E. Castle, V. Chandan, J. Cheville, J.A. Copland, M. Farnell, T. Flotte, N. Giama, H. Thai, M. Kendrick, J. Kocher, K. Kopp, C. Moser, D. Nagorney, D. O’Brien, B.P. O’Neill, T. Patel, G. Petersen, F. Que, M. Rivera, L. Roberts, R. Smallridge, T. Smyrk, M. Stanton, R.H. Thompson, M. Torbenson, J.D. Yang, L. Zhang, F. Brimo, J.A. Ajani, A.M.A. Gonzalez, C. Behrens, J. Bondaruk, R. Broaddus, B. Czerniak, B. Esmaeli, J. Fujimoto, J. Gershenwald, C. Guo, A.J. Lazar, C. Logothetis, F. Meric-Bernstam, C. Moran, L. Ramondetta, D. Rice, A. Sood, P. Tamboli, T. Thompson, P. Troncoso, A. Tsao, I. Wistuba, C. Carter, L. Haydu, P. Hersey, V. Jakrot, H. Kakavand, R. Kefford, K. Lee, G. Long, G. Mann, M. Quinn, R. Saw, R. Scolyer, K. Shannon, A. Spillane, J. Stretch, M. Synott, J. Thompson, J. Wilmott, H. Al-Ahmadie, T.A. Chan, R. Ghossein, A. Gopalan, D.A. Levine, V. Reuter, S. Singer, B. Singh, N.V. Tien, T. Broudy, C. Mirsaidi, P. Nair, P. Drwiega, J. Miller, J. Smith, H. Zaren, J. Park, N.P. Hung, E. Kebebew, W.M. Linehan, A.R. Metwalli, K. Pacak, P.A. Pinto, M. Schiffman, L.S. Schmidt, C.D. Vocke, N. Wentzensen, R. Worrell, H. Yang, M. Moncrieff, C. Goparaju, J. Melamed, H. Pass, N. Botnariuc, I. Caraman, M. Cernat, I. Chemencedji, A. Clipca, S. Doruc, G. Gorincioi, S. Mura, M. Pirtac, I. Stancul, D. Tcaciuc, M. Albert, I. Alexopoulou, A. Arnaout, J. Bartlett, J. Engel, S. Gilbert, J. Parfitt, H. Sekhon, G. Thomas, D.M. Rassl, R.C. Rintoul, C. Bifulco, R. Tamakawa, W. Urba, N. Hayward, H. Timmers, A. Antenucci, F. Facciolo, G. Grazi, M. Marino, R. Merola, R. de Krijger, A. Gimenez-Roqueplo, A. 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Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Liu, Yang;Sethi, Nilay S.;Hinoue, Toshinori;Schneider, Barbara G.;Cherniack, Andrew D.;Sanchez-Vega, Francisco;Seoane, Jose A.;Farshidfar, Farshad;Bowlby, Reanne;Islam, Mirazul;Kim, Jaegil;Chatila, Walid;Akbani, Rehan;Kanchi, Rupa S.;Rabkin, Charles S.;Willis, Joseph E.;Wang, Kenneth K.;McCall, Shannon J.;Mishra, Lopa;Ojesina, Akinyemi I.;Bullman, Susan;Pedamallu, Chandra Sekhar;Lazar, Alexander J.;Sakai, Ryo;Thorsson, Vésteinn;Bass, Adam J.;Laird, Peter W.;Caesar-Johnson, Samantha J.;Demchok, John A.;Felau, Ina;Kasapi, Melpomeni;Ferguson, Martin L.;Hutter, Carolyn M.;Sofia, Heidi J.;Tarnuzzer, Roy;Wang, Zhining;Yang, Liming;Zenklusen, Jean C.;Zhang, Jiashan (Julia);Chudamani, Sudha;Liu, Jia;Lolla, Laxmi;Naresh, Rashi;Pihl, Todd;Sun, Qiang;Wan, Yunhu;Wu, Ye;Cho, Juok;DeFreitas, Timothy;Frazer, Scott;Gehlenborg, Nils;Getz, Gad;Heiman, David I.;Kim, Jaegil;Lawrence, Michael S.;Lin, Pei;Meier, Sam;Noble, Michael S.;Saksena, Gordon;Voet, Doug;Zhang, Hailei;Bernard, Brady;Chambwe, Nyasha;Dhankani, Varsha;Knijnenburg, Theo;Kramer, Roger;Leinonen, Kalle;Liu, Yuexin;Miller, Michael;Reynolds, Sheila;Shmulevich, Ilya;Thorsson, Vesteinn;Zhang, Wei;Akbani, Rehan;Broom, Bradley M.;Hegde, Apurva M.;Ju, Zhenlin;Kanchi, Rupa S.;Korkut, Anil;Li, Jun;Liang, Han;Ling, Shiyun;Liu, Wenbin;Lu, Yiling;Mills, Gordon B.;Ng, Kwok-Shing;Rao, Arvind;Ryan, Michael;Wang, Jing;Weinstein, John N.;Zhang, Jiexin;Abeshouse, Adam;Armenia, Joshua;Chakravarty, Debyani;Chatila, Walid K.;Bruijn, Inode;Gao, Jianjiong;Gross, Benjamin E.;Heins, Zachary J.;Kundra, Ritika;La, Konnor;Ladanyi, Marc;Luna, Augustin;Nissan, Moriah G.;Ochoa, Angelica;Phillips, Sarah M.;Reznik, Ed;Sanchez-Vega, Francisco;Sander, Chris;Schultz, Nikolaus;Sheridan, Robert;Sumer, S. Onur;Sun, Yichao;Taylor, Barry S.;Wang, Jioajiao;Zhang, Hongxin;Anur, Pavana;Peto, Myron;Spellman, Paul;Benz, Christopher;Stuart, Joshua M.;Wong, Christopher K.;Yau, Christina;Hayes, D. Neil;Parker, Joel S.;Wilkerson, Matthew D.;Ally, Adrian;Balasundaram, Miruna;Bowlby, Reanne;Brooks, Denise;Carlsen, Rebecca;Chuah, Eric;Dhalla, Noreen;Holt, Robert;Jones, Steven J. M.;Kasaian, Katayoon;Lee, Darlene;Ma, Yussanne;Marra, Marco A.;Mayo, Michael;Moore, Richard A.;Mungall, Andrew J.;Mungall, Karen;Robertson, A. Gordon;Sadeghi, Sara;Schein, Jacqueline E.;Sipahimalani, Payal;Tam, Angela;Thiessen, Nina;Tse, Kane;Wong, Tina;Berger, Ashton C.;Beroukhim, Rameen;Cherniack, Andrew D.;Cibulskis, Carrie;Gabriel, Stacey B.;Gao, Galen F.;Ha, Gavin;Meyerson, Matthew;Schumacher, Steven E.;Shih, Juliann;Kucherlapati, Melanie H.;Kucherlapati, Raju S.;Baylin, Stephen;Cope, Leslie;Danilova, Ludmila;Bootwalla, Moiz S.;Lai, Phillip H.;Maglinte, Dennis T.;Van Den Berg, David J.;Weisenberger, Daniel J.;Auman, J. Todd;Balu, Saianand;Bodenheimer, Tom;Fan, Cheng;Hoadley, Katherine A.;Hoyle, Alan P.;Jefferys, Stuart R.;Jones, Corbin D.;Meng, Shaowu;Mieczkowski, Piotr A.;Mose, Lisle E.;Perou, Amy H.;Perou, Charles M.;Roach, Jeffrey;Shi, Yan;Simons, Janae V.;Skelly, Tara;Soloway, Matthew G.;Tan, Donghui;Veluvolu, Umadevi;Fan, Huihui;Hinoue, Toshinori;Laird, Peter W.;Shen, Hui;Zhou, Wanding;Bellair, Michelle;Chang, Kyle;Covington, Kyle;Creighton, Chad J.;Dinh, Huyen;Doddapaneni, HarshaVardhan;Donehower, Lawrence A.;Drummond, Jennifer;Gibbs, Richard A.;Glenn, Robert;Hale, Walker;Han, Yi;Hu, Jianhong;Korchina, Viktoriya;Lee, Sandra;Lewis, Lora;Li, Wei;Liu, Xiuping;Morgan, Margaret;Morton, Donna;Muzny, Donna;Santibanez, Jireh;Sheth, Margi;Shinbrot, Eve;Wang, Linghua;Wang, Min;Wheeler, David A.;Xi, Liu;Zhao, Fengmei;Hess, Julian;Appelbaum, Elizabeth L.;Bailey, Matthew;Cordes, Matthew G.;Ding, Li;Fronick, Catrina C.;Fulton, Lucinda A.;Fulton, Robert S.;Kandoth, Cyriac;Mardis, Elaine R.;McLellan, Michael D.;Miller, Christopher A.;Schmidt, Heather K.;Wilson, Richard K.;Crain, Daniel;Curley, Erin;Gardner, Johanna;Lau, Kevin;Mallery, David;Morris, Scott;Paulauskis, Joseph;Penny, Robert;Shelton, Candace;Shelton, Troy;Sherman, Mark;Thompson, Eric;Yena, Peggy;Bowen, Jay;Gastier-Foster, Julie M.;Gerken, Mark;Leraas, Kristen M.;Lichtenberg, Tara M.;Ramirez, Nilsa C.;Wise, Lisa;Zmuda, Erik;Corcoran, Niall;Costello, Tony;Hovens, Christopher;Carvalho, Andre L.;de Carvalho, Ana C.;Fregnani, José H.;Longatto-Filho, Adhemar;Reis, Rui M.;Scapulatempo-Neto, Cristovam;Silveira, Henrique C. S.;Vidal, Daniel O.;Burnette, Andrew;Eschbacher, Jennifer;Hermes, Beth;Noss, Ardene;Singh, Rosy;Anderson, Matthew L.;Castro, Patricia D.;Ittmann, Michael;Huntsman, David;Kohl, Bernard;Le, Xuan;Thorp, Richard;Andry, Chris;Duffy, Elizabeth R.;Lyadov, Vladimir;Paklina, Oxana;Setdikova, Galiya;Shabunin, Alexey;Tavobilov, Mikhail;McPherson, Christopher;Warnick, Ronald;Berkowitz, Ross;Cramer, Daniel;Feltmate, Colleen;Horowitz, Neil;Kibel, Adam;Muto, Michael;Raut, Chandrajit P.;Malykh, Andrei;Barnholtz-Sloan, Jill S.;Barrett, Wendi;Devine, Karen;Fulop, Jordonna;Ostrom, Quinn T.;Shimmel, Kristen;Wolinsky, Yingli;Sloan, Andrew E.;De Rose, Agostino;Giuliante, Felice;Goodman, Marc;Karlan, Beth Y.;Hagedorn, Curt H.;Eckman, John;Harr, Jodi;Myers, Jerome;Tucker, Kelinda;Zach, Leigh Anne;Deyarmin, Brenda;Hu, Hai;Kvecher, Leonid;Larson, Caroline;Mural, Richard J.;Somiari, Stella;Vicha, Ales;Zelinka, Tomas;Bennett, Joseph;Iacocca, Mary;Rabeno, Brenda;Swanson, Patricia;Latour, Mathieu;Lacombe, Louis;Têtu, Bernard;Bergeron, Alain;McGraw, Mary;Staugaitis, Susan M.;Chabot, John;Hibshoosh, Hanina;Sepulveda, Antonia;Su, Tao;Wang, Timothy;Potapova, Olga;Voronina, Olga;Desjardins, Laurence;Mariani, Odette;Roman-Roman, Sergio;Sastre, Xavier;Stern, Marc-Henri;Cheng, Feixiong;Signoretti, Sabina;Berchuck, Andrew;Bigner, Darell;Lipp, Eric;Marks, Jeffrey;McCall, Shannon;McLendon, Roger;Secord, Angeles;Sharp, Alexis;Behera, Madhusmita;Brat, Daniel J.;Chen, Amy;Delman, Keith;Force, Seth;Khuri, Fadlo;Magliocca, Kelly;Maithel, Shishir;Olson, Jeffrey J.;Owonikoko, Taofeek;Pickens, Alan;Ramalingam, Suresh;Shin, Dong M.;Sica, Gabriel;Van Meir, Erwin G.;Zhang, Hongzheng;Eijckenboom, Wil;Gillis, Ad;Korpershoek, Esther;Looijenga, Leendert;Oosterhuis, Wolter;Stoop, Hans;van Kessel, Kim E.;Zwarthoff, Ellen C.;Calatozzolo, Chiara;Cuppini, Lucia;Cuzzubbo, Stefania;F. Dimeco;Finocchiaro, Gaetano;Mattei, Luca;Perin, Alessandro;Pollo, Bianca;Chen, Chu;Houck, John;Lohavanichbutr, Pawadee;Hartmann, Arndt;Stoehr, Christine;Stoehr, Robert;Taubert, Helge;Wach, Sven;Wullich, Bernd;Kycler, Witold;Murawa, Dawid;Wiznerowicz, Maciej;Chung, Ki;Edenfield, W. Jeffrey;Martin, Julie;Baudin, Eric;Bubley, Glenn;Bueno, Raphael;De Rienzo, Assunta;Richards, William G.;Kalkanis, Steven;Mikkelsen, Tom;Noushmehr, Houtan;Scarpace, Lisa;Girard, Nicolas;Aymerich, Marta;Campo, Elias;Giné, Eva;Guillermo, Armando López;Van Bang, Nguyen;Hanh, Phan Thi;Phu, Bui Duc;Tang, Yufang;Colman, Howard;Evason, Kimberley;Dottino, Peter R.;Martignetti, John A.;Gabra, Hani;Juhl, Hartmut;Akeredolu, Teniola;Stepa, Serghei;Hoon, Dave;Ahn, Keunsoo;Kang, Koo Jeong;Beuschlein, Felix;Breggia, Anne;Birrer, Michael;Bell, Debra;Borad, Mitesh;Bryce, Alan H.;Castle, Erik;Chandan, Vishal;Cheville, John;Copland, John A.;Farnell, Michael;Flotte, Thomas;Giama, Nasra;Ho, Thai;Kendrick, Michael;Kocher, Jean-Pierre;Kopp, Karla;Moser, Catherine;Nagorney, David;O’Brien, Daniel;O’Neill, Brian Patrick;Patel, Tushar;Petersen, Gloria;Que, Florencia;Rivera, Michael;Roberts, Lewis;Smallridge, Robert;Smyrk, Thomas;Stanton, Melissa;Thompson, R. Houston;Torbenson, Michael;Yang, Ju Dong;Zhang, Lizhi;Brimo, Fadi;Ajani, Jaffer A.;Gonzalez, Ana Maria Angulo;Behrens, Carmen;Bondaruk, Jolanta;Broaddus, Russell;Czerniak, Bogdan;Esmaeli, Bita;Fujimoto, Junya;Gershenwald, Jeffrey;Guo, Charles;Lazar, Alexander J.;Logothetis, Christopher;Meric-Bernstam, Funda;Moran, Cesar;Ramondetta, Lois;Rice, David;Sood, Anil;Tamboli, Pheroze;Thompson, Timothy;Troncoso, Patricia;Tsao, Anne;Wistuba, Ignacio;Carter, Candace;Haydu, Lauren;Hersey, Peter;Jakrot, Valerie;Kakavand, Hojabr;Kefford, Richard;Lee, Kenneth;Long, Georgina;Mann, Graham;Quinn, Michael;Saw, Robyn;Scolyer, Richard;Shannon, Kerwin;Spillane, Andrew;Stretch, Jonathan;Synott, Maria;Thompson, John;Wilmott, James;Al-Ahmadie, Hikmat;Chan, Timothy A.;Ghossein, Ronald;Gopalan, Anuradha;Levine, Douglas A.;Reuter, Victor;Singer, Samuel;Singh, Bhuvanesh;Tien, Nguyen Viet;Broudy, Thomas;Mirsaidi, Cyrus;Nair, Praveen;Drwiega, Paul;Miller, Judy;Smith, Jennifer;Zaren, Howard;Park, Joong-Won;Hung, Nguyen Phi;Kebebew, Electron;Linehan, W. Marston;Metwalli, Adam R.;Pacak, Karel;Pinto, Peter A.;Schiffman, Mark;Schmidt, Laura S.;Vocke, Cathy D.;Wentzensen, Nicolas;Worrell, Robert;Yang, Hannah;Moncrieff, Marc;Goparaju, Chandra;Melamed, Jonathan;Pass, Harvey;Botnariuc, Natalia;Caraman, Irina;Cernat, Mircea;Chemencedji, Inga;Clipca, Adrian;Doruc, Serghei;Gorincioi, Ghenadie;Mura, Sergiu;Pirtac, Maria;Stancul, Irina;Tcaciuc, Diana;Albert, Monique;Alexopoulou, Iakovina;Arnaout, Angel;Bartlett, John;Engel, Jay;Gilbert, Sebastien;Parfitt, Jeremy;Sekhon, Harman;Thomas, George;Rassl, Doris M.;Rintoul, Robert C.;Bifulco, Carlo;Tamakawa, Raina;Urba, Walter;Hayward, Nicholas;Timmers, Henri;Antenucci, Anna;Facciolo, Francesco;Grazi, Gianluca;Marino, Mirella;Merola, Roberta;de Krijger, Ronald;Gimenez-Roqueplo, Anne-Paule;Piché, Alain;Chevalier, Simone;McKercher, Ginette;Birsoy, Kivanc;Barnett, Gene;Brewer, Cathy;Farver, Carol;Naska, Theresa;Pennell, Nathan A.;Raymond, Daniel;Schilero, Cathy;Smolenski, Kathy;Williams, Felicia;Morrison, Carl;Borgia, Jeffrey A.;Liptay, Michael J.;Pool, Mark;Seder, Christopher W.;Junker, Kerstin;Omberg, Larsson;Dinkin, Mikhail;Manikhas, George;Alvaro, Domenico;Bragazzi, Maria Consiglia;Cardinale, Vincenzo;Carpino, Guido;Gaudio, Eugenio;Chesla, David;Cottingham, Sandra;Dubina, Michael;Moiseenko, Fedor;Dhanasekaran, Renumathy;Becker, Karl-Friedrich;Janssen, Klaus-Peter;Slotta-Huspenina, Julia;Abdel-Rahman, Mohamed H.;Aziz, Dina;Bell, Sue;Cebulla, Colleen M.;Davis, Amy;Duell, Rebecca;Elder, J. 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2018

Abstract

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1.

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Scheda completa

Scheda completa (DC)

	Parole chiave
	
				cancer; colon; colorectal; epigenetic; esophagus; genomic; methylation; rectum; stomach; tumor
			
	Settori scientifico-disciplinari dell'articolo (sola visualizzazione)
	
				Settore MED/27 - Neurochirurgia
			
	Data di pubblicazione
	
				9-apr-2018
			
	Rivista in ANCE
	
				CANCER CELL
			
	DOI
	
				https://dx.doi.org/10.1016/j.ccell.2018.03.010
			
	Tipologia
	
				Article (author)
			
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				01 - Articolo su periodico

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