Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

Michele Ceccarelli; Floris P. Barthel; Tathiane M. Malta; Thais S. Sabedot; Sofie R. Salama; Bradley A. Murray; Olena Morozova; Yulia Newton; Amie Radenbaugh; Stefano M. Pagnotta; Samreen Anjum; Jiguang Wang; Ganiraju Manyam; Pietro Zoppoli; Shiyun Ling; Arjun A. Rao; Mia Grifford; Andrew D. Cherniack; Hailei Zhang; Laila Poisson; Carlos Gilberto Carlotti; Daniela Pretti Da Cunha Tirapelli; Arvind Rao; Tom Mikkelsen; Ching C. Lau; W. K.Alfred Yung; Raul Rabadan; Jason Huse; Daniel J. Brat; Norman L. Lehman; Jill S. Barnholtz-Sloan; Siyuan Zheng; Kenneth Hess; Ganesh Rao; Matthew Meyerson; Rameen Beroukhim; Lee Cooper; Rehan Akbani; Margaret Wrensch; David Haussler; Kenneth D. Aldape; Peter W. Laird; David H. Gutmann; Houtan Noushmehr; Harindra Arachchi; J. Todd Auman; Miruna Balasundaram; Saianand Balu; Gene Barnett; Stephen Baylin; Sue Bell; Christopher Benz; Natalie Bir; Keith L. Black; Tom Bodenheimer; Lori Boice; Moiz S. Bootwalla; Jay Bowen; Christopher A. Bristow; Yaron S.N. Butterfield; Qing Rong Chen; Lynda Chin; Juok Cho; Eric Chuah; Sudha Chudamani; Simon G. Coetzee; Mark L. Cohen; Howard Colman; Marta Couce; Fulvio D'Angelo; Tanja Davidsen; Amy Davis; John A. Demchok; Karen Devine; Li Ding; Rebecca Duell; J. Bradley Elder; Jennifer M. Eschbacher; Ashley Fehrenbach; Martin Ferguson; Scott Frazer; Gregory Fuller; Jordonna Fulop; Stacey B. Gabriel; Luciano Garofano; Julie M. Gastier-Foster; Nils Gehlenborg; Mark Gerken; Gad Getz; Caterina Giannini; William J. Gibson; Angela Hadjipanayis; D. Neil Hayes; David I. Heiman; Beth Hermes; Joe Hilty; Katherine A. Hoadley; Alan P. Hoyle; Mei Huang; Stuart R. Jefferys; Corbin D. Jones; Steven J.M. Jones; Zhenlin Ju; Alison Kastl; Ady Kendler; Jaegil Kim; Raju Kucherlapati; Phillip H. Lai; Michael S. Lawrence; Semin Lee; Kristen M. Leraas; Tara M. Lichtenberg; Pei Lin; Yuexin Liu; Jia Liu; Julia Y. Ljubimova; Yiling Lu; Yussanne Ma; Dennis T. Maglinte; Harshad S. Mahadeshwar; Marco A. Marra; Mary McGraw; Christopher McPherson; Shaowu Meng; Piotr A. Mieczkowski; C. Ryan Miller; Gordon B. Mills; Richard A. Moore; Lisle E. Mose; Andrew J. Mungall; Rashi Naresh; Theresa Naska; Luciano Neder; Michael S. Noble; Ardene Noss; Brian Patrick O'Neill; Quinn T. Ostrom; Cheryl Palmer; Angeliki Pantazi; Michael Parfenov; Peter J. Park; Joel S. Parker; Charles M. Perou; Christopher R. Pierson; Todd Pihl; Alexei Protopopov; Amie Radenbaugh; Nilsa C. Ramirez; W. Kimryn Rathmell; Xiaojia Ren; Jeffrey Roach; A. Gordon Robertson; Gordon Saksena; Jacqueline E. Schein; Steven E. Schumacher; Jonathan Seidman; Kelly Senecal; Sahil Seth; Hui Shen; Yan Shi; Juliann Shih; Kristen Shimmel; Hugues Sicotte; Suzanne Sifri; Tiago Silva; Janae V. Simons; Rosy Singh; Tara Skelly; Andrew E. Sloan; Heidi J. Sofia; Matthew G. Soloway; Xingzhi Song; Carrie Sougnez; Camila Souza; Susan M. Staugaitis; Huandong Sun; Charlie Sun; Donghui Tan; Jiabin Tang; Yufang Tang; Leigh Thorne; Felipe Amstalden Trevisan; Timothy Triche; David J. Van Den Berg; Umadevi Veluvolu; Doug Voet; Yunhu Wan; Zhining Wang; Ronald Warnick; John N. Weinstein; Daniel J. Weisenberger; Matthew D. Wilkerson; Felicia Williams; Lisa Wise; Yingli Wolinsky; Junyuan Wu; Andrew W. Xu; Lixing Yang; Liming Yang; Travis I. Zack; Jean C. Zenklusen; Jianhua Zhang; Wei Zhang; Jiashan Zhang; Erik Zmuda; Houtan Noushmehr; Antonio Iavarone; Roel G.W. Verhaak

doi:10.1016/j.cell.2015.12.028

Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

Michele Ceccarelli, Floris P. Barthel, Tathiane M. Malta, Thais S. Sabedot, Sofie R. Salama, Bradley A. Murray, Olena Morozova, Yulia Newton, Amie Radenbaugh, Stefano M. Pagnotta, Samreen Anjum, Jiguang Wang, Ganiraju Manyam, Pietro Zoppoli, Shiyun Ling, Arjun A. Rao, Mia Grifford, Andrew D. Cherniack, Hailei Zhang, Laila PoissonCarlos Gilberto Carlotti, Daniela Pretti Da Cunha Tirapelli, Arvind Rao, Tom Mikkelsen, Ching C. Lau, W. K.Alfred Yung, Raul Rabadan, Jason Huse, Daniel J. Brat, Norman L. Lehman, Jill S. Barnholtz-Sloan, Siyuan Zheng, Kenneth Hess, Ganesh Rao, Matthew Meyerson, Rameen Beroukhim, Lee Cooper, Rehan Akbani, Margaret Wrensch, David Haussler, Kenneth D. Aldape, Peter W. Laird, David H. Gutmann, Houtan Noushmehr, Harindra Arachchi, J. Todd Auman, Miruna Balasundaram, Saianand Balu, Gene Barnett, Stephen Baylin, Sue Bell, Christopher Benz, Natalie Bir, Keith L. Black, Tom Bodenheimer, Lori Boice, Moiz S. Bootwalla, Jay Bowen, Christopher A. Bristow, Yaron S.N. Butterfield, Qing Rong Chen, Lynda Chin, Juok Cho, Eric Chuah, Sudha Chudamani, Simon G. Coetzee, Mark L. Cohen, Howard Colman, Marta Couce, Fulvio D'Angelo, Tanja Davidsen, Amy Davis, John A. Demchok, Karen Devine, Li Ding, Rebecca Duell, J. Bradley Elder, Jennifer M. Eschbacher, Ashley Fehrenbach, Martin Ferguson, Scott Frazer, Gregory Fuller, Jordonna Fulop, Stacey B. Gabriel, Luciano Garofano, Julie M. Gastier-Foster, Nils Gehlenborg, Mark Gerken, Gad Getz, Caterina Giannini, William J. Gibson, Angela Hadjipanayis, D. Neil Hayes, David I. Heiman, Beth Hermes, Joe Hilty, Katherine A. Hoadley, Alan P. Hoyle, Mei Huang, Stuart R. Jefferys, Corbin D. Jones, Steven J.M. Jones, Zhenlin Ju, Alison Kastl, Ady Kendler, Jaegil Kim, Raju Kucherlapati, Phillip H. Lai, Michael S. Lawrence, Semin Lee, Kristen M. Leraas, Tara M. Lichtenberg, Pei Lin, Yuexin Liu, Jia Liu, Julia Y. Ljubimova, Yiling Lu, Yussanne Ma, Dennis T. Maglinte, Harshad S. Mahadeshwar, Marco A. Marra, Mary McGraw, Christopher McPherson, Shaowu Meng, Piotr A. Mieczkowski, C. Ryan Miller, Gordon B. Mills, Richard A. Moore, Lisle E. Mose, Andrew J. Mungall, Rashi Naresh, Theresa Naska, Luciano Neder, Michael S. Noble, Ardene Noss, Brian Patrick O'Neill, Quinn T. Ostrom, Cheryl Palmer, Angeliki Pantazi, Michael Parfenov, Peter J. Park, Joel S. Parker, Charles M. Perou, Christopher R. Pierson, Todd Pihl, Alexei Protopopov, Amie Radenbaugh, Nilsa C. Ramirez, W. Kimryn Rathmell, Xiaojia Ren, Jeffrey Roach, A. Gordon Robertson, Gordon Saksena, Jacqueline E. Schein, Steven E. Schumacher, Jonathan Seidman, Kelly Senecal, Sahil Seth, Hui Shen, Yan Shi, Juliann Shih, Kristen Shimmel, Hugues Sicotte, Suzanne Sifri, Tiago Silva, Janae V. Simons, Rosy Singh, Tara Skelly, Andrew E. Sloan, Heidi J. Sofia, Matthew G. Soloway, Xingzhi Song, Carrie Sougnez, Camila Souza, Susan M. Staugaitis, Huandong Sun, Charlie Sun, Donghui Tan, Jiabin Tang, Yufang Tang, Leigh Thorne, Felipe Amstalden Trevisan, Timothy Triche, David J. Van Den Berg, Umadevi Veluvolu, Doug Voet, Yunhu Wan, Zhining Wang, Ronald Warnick, John N. Weinstein, Daniel J. Weisenberger, Matthew D. Wilkerson, Felicia Williams, Lisa Wise, Yingli Wolinsky, Junyuan Wu, Andrew W. Xu, Lixing Yang, Liming Yang, Travis I. Zack, Jean C. Zenklusen, Jianhua Zhang, Wei Zhang, Jiashan Zhang, Erik Zmuda, Houtan Noushmehr, Antonio Iavarone, Roel G.W. Verhaak

Research output: Contribution to journal › Article › peer-review

1279 Scopus citations

Abstract

Summary Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.

Original language	English (US)
Pages (from-to)	550-563
Number of pages	14
Journal	Cell
Volume	164
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2015.12.028
State	Published - Jan 28 2016

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

Access to Document

10.1016/j.cell.2015.12.028

Cite this

Ceccarelli, M., Barthel, F. P., Malta, T. M., Sabedot, T. S., Salama, S. R., Murray, B. A., Morozova, O., Newton, Y., Radenbaugh, A., Pagnotta, S. M., Anjum, S., Wang, J., Manyam, G., Zoppoli, P., Ling, S., Rao, A. A., Grifford, M., Cherniack, A. D., Zhang, H., ... Verhaak, R. G. W. (2016). Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. Cell, 164(3), 550-563. https://doi.org/10.1016/j.cell.2015.12.028

Ceccarelli, M, Barthel, FP, Malta, TM, Sabedot, TS, Salama, SR, Murray, BA, Morozova, O, Newton, Y, Radenbaugh, A, Pagnotta, SM, Anjum, S, Wang, J, Manyam, G, Zoppoli, P, Ling, S, Rao, AA, Grifford, M, Cherniack, AD, Zhang, H, Poisson, L, Carlotti, CG, Tirapelli, DPDC, Rao, A, Mikkelsen, T, Lau, CC, Yung, WKA, Rabadan, R, Huse, J, Brat, DJ, Lehman, NL, Barnholtz-Sloan, JS, Zheng, S, Hess, K, Rao, G, Meyerson, M, Beroukhim, R, Cooper, L, Akbani, R, Wrensch, M, Haussler, D, Aldape, KD, Laird, PW, Gutmann, DH, Noushmehr, H, Arachchi, H, Auman, JT, Balasundaram, M, Balu, S, Barnett, G, Baylin, S, Bell, S, Benz, C, Bir, N, Black, KL, Bodenheimer, T, Boice, L, Bootwalla, MS, Bowen, J, Bristow, CA, Butterfield, YSN, Chen, QR, Chin, L, Cho, J, Chuah, E, Chudamani, S, Coetzee, SG, Cohen, ML, Colman, H, Couce, M, D'Angelo, F, Davidsen, T, Davis, A, Demchok, JA, Devine, K, Ding, L, Duell, R, Elder, JB, Eschbacher, JM, Fehrenbach, A, Ferguson, M, Frazer, S, Fuller, G, Fulop, J, Gabriel, SB, Garofano, L, Gastier-Foster, JM, Gehlenborg, N, Gerken, M, Getz, G, Giannini, C, Gibson, WJ, Hadjipanayis, A, Hayes, DN, Heiman, DI, Hermes, B, Hilty, J, Hoadley, KA, Hoyle, AP, Huang, M, Jefferys, SR, Jones, CD, Jones, SJM, Ju, Z, Kastl, A, Kendler, A, Kim, J, Kucherlapati, R, Lai, PH, Lawrence, MS, Lee, S, Leraas, KM, Lichtenberg, TM, Lin, P, Liu, Y, Liu, J, Ljubimova, JY, Lu, Y, Ma, Y, Maglinte, DT, Mahadeshwar, HS, Marra, MA, McGraw, M, McPherson, C, Meng, S, Mieczkowski, PA, Miller, CR, Mills, GB, Moore, RA, Mose, LE, Mungall, AJ, Naresh, R, Naska, T, Neder, L, Noble, MS, Noss, A, O'Neill, BP, Ostrom, QT, Palmer, C, Pantazi, A, Parfenov, M, Park, PJ, Parker, JS, Perou, CM, Pierson, CR, Pihl, T, Protopopov, A, Radenbaugh, A, Ramirez, NC, Rathmell, WK, Ren, X, Roach, J, Robertson, AG, Saksena, G, Schein, JE, Schumacher, SE, Seidman, J, Senecal, K, Seth, S, Shen, H, Shi, Y, Shih, J, Shimmel, K, Sicotte, H, Sifri, S, Silva, T, Simons, JV, Singh, R, Skelly, T, Sloan, AE, Sofia, HJ, Soloway, MG, Song, X, Sougnez, C, Souza, C, Staugaitis, SM, Sun, H, Sun, C, Tan, D, Tang, J, Tang, Y, Thorne, L, Trevisan, FA, Triche, T, Van Den Berg, DJ, Veluvolu, U, Voet, D, Wan, Y, Wang, Z, Warnick, R, Weinstein, JN, Weisenberger, DJ, Wilkerson, MD, Williams, F, Wise, L, Wolinsky, Y, Wu, J, Xu, AW, Yang, L, Yang, L, Zack, TI, Zenklusen, JC, Zhang, J, Zhang, W, Zhang, J, Zmuda, E, Noushmehr, H, Iavarone, A & Verhaak, RGW 2016, 'Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma', Cell, vol. 164, no. 3, pp. 550-563. https://doi.org/10.1016/j.cell.2015.12.028

@article{a4d7744d2670442fa5740e07b3d2e932,

title = "Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma",

abstract = "Summary Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.",

author = "Michele Ceccarelli and Barthel, {Floris P.} and Malta, {Tathiane M.} and Sabedot, {Thais S.} and Salama, {Sofie R.} and Murray, {Bradley A.} and Olena Morozova and Yulia Newton and Amie Radenbaugh and Pagnotta, {Stefano M.} and Samreen Anjum and Jiguang Wang and Ganiraju Manyam and Pietro Zoppoli and Shiyun Ling and Rao, {Arjun A.} and Mia Grifford and Cherniack, {Andrew D.} and Hailei Zhang and Laila Poisson and Carlotti, {Carlos Gilberto} and Tirapelli, {Daniela Pretti Da Cunha} and Arvind Rao and Tom Mikkelsen and Lau, {Ching C.} and Yung, {W. K.Alfred} and Raul Rabadan and Jason Huse and Brat, {Daniel J.} and Lehman, {Norman L.} and Barnholtz-Sloan, {Jill S.} and Siyuan Zheng and Kenneth Hess and Ganesh Rao and Matthew Meyerson and Rameen Beroukhim and Lee Cooper and Rehan Akbani and Margaret Wrensch and David Haussler and Aldape, {Kenneth D.} and Laird, {Peter W.} and Gutmann, {David H.} and Houtan Noushmehr and Harindra Arachchi and Auman, {J. Todd} and Miruna Balasundaram and Saianand Balu and Gene Barnett and Stephen Baylin and Sue Bell and Christopher Benz and Natalie Bir and Black, {Keith L.} and Tom Bodenheimer and Lori Boice and Bootwalla, {Moiz S.} and Jay Bowen and Bristow, {Christopher A.} and Butterfield, {Yaron S.N.} and Chen, {Qing Rong} and Lynda Chin and Juok Cho and Eric Chuah and Sudha Chudamani and Coetzee, {Simon G.} and Cohen, {Mark L.} and Howard Colman and Marta Couce and Fulvio D'Angelo and Tanja Davidsen and Amy Davis and Demchok, {John A.} and Karen Devine and Li Ding and Rebecca Duell and Elder, {J. Bradley} and Eschbacher, {Jennifer M.} and Ashley Fehrenbach and Martin Ferguson and Scott Frazer and Gregory Fuller and Jordonna Fulop and Gabriel, {Stacey B.} and Luciano Garofano and Gastier-Foster, {Julie M.} and Nils Gehlenborg and Mark Gerken and Gad Getz and Caterina Giannini and Gibson, {William J.} and Angela Hadjipanayis and Hayes, {D. Neil} and Heiman, {David I.} and Beth Hermes and Joe Hilty and Hoadley, {Katherine A.} and Hoyle, {Alan P.} and Mei Huang and Jefferys, {Stuart R.} and Jones, {Corbin D.} and Jones, {Steven J.M.} and Zhenlin Ju and Alison Kastl and Ady Kendler and Jaegil Kim and Raju Kucherlapati and Lai, {Phillip H.} and Lawrence, {Michael S.} and Semin Lee and Leraas, {Kristen M.} and Lichtenberg, {Tara M.} and Pei Lin and Yuexin Liu and Jia Liu and Ljubimova, {Julia Y.} and Yiling Lu and Yussanne Ma and Maglinte, {Dennis T.} and Mahadeshwar, {Harshad S.} and Marra, {Marco A.} and Mary McGraw and Christopher McPherson and Shaowu Meng and Mieczkowski, {Piotr A.} and Miller, {C. Ryan} and Mills, {Gordon B.} and Moore, {Richard A.} and Mose, {Lisle E.} and Mungall, {Andrew J.} and Rashi Naresh and Theresa Naska and Luciano Neder and Noble, {Michael S.} and Ardene Noss and O'Neill, {Brian Patrick} and Ostrom, {Quinn T.} and Cheryl Palmer and Angeliki Pantazi and Michael Parfenov and Park, {Peter J.} and Parker, {Joel S.} and Perou, {Charles M.} and Pierson, {Christopher R.} and Todd Pihl and Alexei Protopopov and Amie Radenbaugh and Ramirez, {Nilsa C.} and Rathmell, {W. Kimryn} and Xiaojia Ren and Jeffrey Roach and Robertson, {A. Gordon} and Gordon Saksena and Schein, {Jacqueline E.} and Schumacher, {Steven E.} and Jonathan Seidman and Kelly Senecal and Sahil Seth and Hui Shen and Yan Shi and Juliann Shih and Kristen Shimmel and Hugues Sicotte and Suzanne Sifri and Tiago Silva and Simons, {Janae V.} and Rosy Singh and Tara Skelly and Sloan, {Andrew E.} and Sofia, {Heidi J.} and Soloway, {Matthew G.} and Xingzhi Song and Carrie Sougnez and Camila Souza and Staugaitis, {Susan M.} and Huandong Sun and Charlie Sun and Donghui Tan and Jiabin Tang and Yufang Tang and Leigh Thorne and Trevisan, {Felipe Amstalden} and Timothy Triche and {Van Den Berg}, {David J.} and Umadevi Veluvolu and Doug Voet and Yunhu Wan and Zhining Wang and Ronald Warnick and Weinstein, {John N.} and Weisenberger, {Daniel J.} and Wilkerson, {Matthew D.} and Felicia Williams and Lisa Wise and Yingli Wolinsky and Junyuan Wu and Xu, {Andrew W.} and Lixing Yang and Liming Yang and Zack, {Travis I.} and Zenklusen, {Jean C.} and Jianhua Zhang and Wei Zhang and Jiashan Zhang and Erik Zmuda and Houtan Noushmehr and Antonio Iavarone and Verhaak, {Roel G.W.}",

note = "Funding Information: This study was supported by NIH grants U24CA143883, U24CA143858, U24CA143840, U24CA143799, U24CA143835, U24CA143845, U24CA143882, U24CA143867, U24CA143866, U24CA143848, U24CA144025, U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544, U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA126563, U24CA143731, U24CA143843, P30CA016672, P50 CA127001, U54CA193313, R01CA179044, R01CA185486, R01 CA190121, and P01 CA085878; Cancer Prevention & Research Institute of Texas (CPRIT) R140606; and S{\~a}o Paulo Research Foundation (FAPESP) 2014/02245-3, 2015/07925-5, 2015/02844-7, and 2015/08321-3. D.J.W. is a consultant for Zymo Research Corporation. R.B. is a consultant for and received grant funding from Novartis. A.D.C. and M.M. received grant support from Bayer. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = jan,

day = "28",

doi = "10.1016/j.cell.2015.12.028",

language = "English (US)",

volume = "164",

pages = "550--563",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

AU - Ceccarelli, Michele

AU - Barthel, Floris P.

AU - Malta, Tathiane M.

AU - Sabedot, Thais S.

AU - Salama, Sofie R.

AU - Murray, Bradley A.

AU - Morozova, Olena

AU - Newton, Yulia

AU - Radenbaugh, Amie

AU - Pagnotta, Stefano M.

AU - Anjum, Samreen

AU - Wang, Jiguang

AU - Manyam, Ganiraju

AU - Zoppoli, Pietro

AU - Ling, Shiyun

AU - Rao, Arjun A.

AU - Grifford, Mia

AU - Cherniack, Andrew D.

AU - Zhang, Hailei

AU - Poisson, Laila

AU - Carlotti, Carlos Gilberto

AU - Tirapelli, Daniela Pretti Da Cunha

AU - Rao, Arvind

AU - Mikkelsen, Tom

AU - Lau, Ching C.

AU - Yung, W. K.Alfred

AU - Rabadan, Raul

AU - Huse, Jason

AU - Brat, Daniel J.

AU - Lehman, Norman L.

AU - Barnholtz-Sloan, Jill S.

AU - Zheng, Siyuan

AU - Hess, Kenneth

AU - Rao, Ganesh

AU - Meyerson, Matthew

AU - Beroukhim, Rameen

AU - Cooper, Lee

AU - Akbani, Rehan

AU - Wrensch, Margaret

AU - Haussler, David

AU - Aldape, Kenneth D.

AU - Laird, Peter W.

AU - Gutmann, David H.

AU - Noushmehr, Houtan

AU - Arachchi, Harindra

AU - Auman, J. Todd

AU - Balasundaram, Miruna

AU - Balu, Saianand

AU - Barnett, Gene

AU - Baylin, Stephen

AU - Bell, Sue

AU - Benz, Christopher

AU - Bir, Natalie

AU - Black, Keith L.

AU - Bodenheimer, Tom

AU - Boice, Lori

AU - Bootwalla, Moiz S.

AU - Bowen, Jay

AU - Bristow, Christopher A.

AU - Butterfield, Yaron S.N.

AU - Chen, Qing Rong

AU - Chin, Lynda

AU - Cho, Juok

AU - Chuah, Eric

AU - Chudamani, Sudha

AU - Coetzee, Simon G.

AU - Cohen, Mark L.

AU - Colman, Howard

AU - Couce, Marta

AU - D'Angelo, Fulvio

AU - Davidsen, Tanja

AU - Davis, Amy

AU - Demchok, John A.

AU - Devine, Karen

AU - Ding, Li

AU - Duell, Rebecca

AU - Elder, J. Bradley

AU - Eschbacher, Jennifer M.

AU - Fehrenbach, Ashley

AU - Ferguson, Martin

AU - Frazer, Scott

AU - Fuller, Gregory

AU - Fulop, Jordonna

AU - Gabriel, Stacey B.

AU - Garofano, Luciano

AU - Gastier-Foster, Julie M.

AU - Gehlenborg, Nils

AU - Gerken, Mark

AU - Getz, Gad

AU - Giannini, Caterina

AU - Gibson, William J.

AU - Hadjipanayis, Angela

AU - Hayes, D. Neil

AU - Heiman, David I.

AU - Hermes, Beth

AU - Hilty, Joe

AU - Hoadley, Katherine A.

AU - Hoyle, Alan P.

AU - Huang, Mei

AU - Jefferys, Stuart R.

AU - Jones, Corbin D.

AU - Jones, Steven J.M.

AU - Ju, Zhenlin

AU - Kastl, Alison

AU - Kendler, Ady

AU - Kim, Jaegil

AU - Kucherlapati, Raju

AU - Lai, Phillip H.

AU - Lawrence, Michael S.

AU - Lee, Semin

AU - Leraas, Kristen M.

AU - Lichtenberg, Tara M.

AU - Lin, Pei

AU - Liu, Yuexin

AU - Liu, Jia

AU - Ljubimova, Julia Y.

AU - Lu, Yiling

AU - Ma, Yussanne

AU - Maglinte, Dennis T.

AU - Mahadeshwar, Harshad S.

AU - Marra, Marco A.

AU - McGraw, Mary

AU - McPherson, Christopher

AU - Meng, Shaowu

AU - Mieczkowski, Piotr A.

AU - Miller, C. Ryan

AU - Mills, Gordon B.

AU - Moore, Richard A.

AU - Mose, Lisle E.

AU - Mungall, Andrew J.

AU - Naresh, Rashi

AU - Naska, Theresa

AU - Neder, Luciano

AU - Noble, Michael S.

AU - Noss, Ardene

AU - O'Neill, Brian Patrick

AU - Ostrom, Quinn T.

AU - Palmer, Cheryl

AU - Pantazi, Angeliki

AU - Parfenov, Michael

AU - Park, Peter J.

AU - Parker, Joel S.

AU - Perou, Charles M.

AU - Pierson, Christopher R.

AU - Pihl, Todd

AU - Protopopov, Alexei

AU - Radenbaugh, Amie

AU - Ramirez, Nilsa C.

AU - Rathmell, W. Kimryn

AU - Ren, Xiaojia

AU - Roach, Jeffrey

AU - Robertson, A. Gordon

AU - Saksena, Gordon

AU - Schein, Jacqueline E.

AU - Schumacher, Steven E.

AU - Seidman, Jonathan

AU - Senecal, Kelly

AU - Seth, Sahil

AU - Shen, Hui

AU - Shi, Yan

AU - Shih, Juliann

AU - Shimmel, Kristen

AU - Sicotte, Hugues

AU - Sifri, Suzanne

AU - Silva, Tiago

AU - Simons, Janae V.

AU - Singh, Rosy

AU - Skelly, Tara

AU - Sloan, Andrew E.

AU - Sofia, Heidi J.

AU - Soloway, Matthew G.

AU - Song, Xingzhi

AU - Sougnez, Carrie

AU - Souza, Camila

AU - Staugaitis, Susan M.

AU - Sun, Huandong

AU - Sun, Charlie

AU - Tan, Donghui

AU - Tang, Jiabin

AU - Tang, Yufang

AU - Thorne, Leigh

AU - Trevisan, Felipe Amstalden

AU - Triche, Timothy

AU - Van Den Berg, David J.

AU - Veluvolu, Umadevi

AU - Voet, Doug

AU - Wan, Yunhu

AU - Wang, Zhining

AU - Warnick, Ronald

AU - Weinstein, John N.

AU - Weisenberger, Daniel J.

AU - Wilkerson, Matthew D.

AU - Williams, Felicia

AU - Wise, Lisa

AU - Wolinsky, Yingli

AU - Wu, Junyuan

AU - Xu, Andrew W.

AU - Yang, Lixing

AU - Yang, Liming

AU - Zack, Travis I.

AU - Zenklusen, Jean C.

AU - Zhang, Jianhua

AU - Zhang, Wei

AU - Zhang, Jiashan

AU - Zmuda, Erik

AU - Noushmehr, Houtan

AU - Iavarone, Antonio

AU - Verhaak, Roel G.W.

N1 - Funding Information: This study was supported by NIH grants U24CA143883, U24CA143858, U24CA143840, U24CA143799, U24CA143835, U24CA143845, U24CA143882, U24CA143867, U24CA143866, U24CA143848, U24CA144025, U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544, U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA126563, U24CA143731, U24CA143843, P30CA016672, P50 CA127001, U54CA193313, R01CA179044, R01CA185486, R01 CA190121, and P01 CA085878; Cancer Prevention & Research Institute of Texas (CPRIT) R140606; and São Paulo Research Foundation (FAPESP) 2014/02245-3, 2015/07925-5, 2015/02844-7, and 2015/08321-3. D.J.W. is a consultant for Zymo Research Corporation. R.B. is a consultant for and received grant funding from Novartis. A.D.C. and M.M. received grant support from Bayer. Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/1/28

Y1 - 2016/1/28

N2 - Summary Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.

AB - Summary Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.

UR - http://www.scopus.com/inward/record.url?scp=84955561447&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955561447&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2015.12.028

DO - 10.1016/j.cell.2015.12.028

M3 - Article

C2 - 26824661

AN - SCOPUS:84955561447

SN - 0092-8674

VL - 164

SP - 550

EP - 563

JO - Cell

JF - Cell

IS - 3

ER -

Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

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