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 & 188 others 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 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 journalArticle

509 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)550-563
Number of pages14
JournalCell
Volume164
Issue number3
DOIs
StatePublished - Jan 28 2016
Externally publishedYes

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Glioma
Genes
Genome
Mutation
Atlases
Telomere
Astrocytoma
DNA Methylation
DNA
Neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ceccarelli, M., Barthel, F. P., Malta, T. M., Sabedot, T. S., Salama, S. R., Murray, B. A., ... 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

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

In: Cell, Vol. 164, No. 3, 28.01.2016, p. 550-563.

Research output: Contribution to journalArticle

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, G, 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
Ceccarelli M, Barthel FP, Malta TM, Sabedot TS, Salama SR, Murray BA et al. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. Cell. 2016 Jan 28;164(3):550-563. https://doi.org/10.1016/j.cell.2015.12.028
Ceccarelli, Michele ; Barthel, Floris P. ; Malta, Tathiane M. ; Sabedot, Thais S. ; Salama, Sofie R. ; Murray, Bradley A. ; Morozova, Olena ; Newton, Yulia ; Radenbaugh, Amie ; Pagnotta, Stefano M. ; Anjum, Samreen ; Wang, Jiguang ; Manyam, Ganiraju ; Zoppoli, Pietro ; Ling, Shiyun ; Rao, Arjun A. ; Grifford, Mia ; Cherniack, Andrew D. ; Zhang, Hailei ; Poisson, Laila ; Carlotti, Carlos Gilberto ; Tirapelli, Daniela Pretti Da Cunha ; Rao, Arvind ; Mikkelsen, Tom ; Lau, Ching C. ; Yung, W. K.Alfred ; Rabadan, Raul ; Huse, Jason ; Brat, Daniel J. ; Lehman, Norman L. ; Barnholtz-Sloan, Jill S. ; Zheng, Siyuan ; Hess, Kenneth ; Rao, Ganesh ; Meyerson, Matthew ; Beroukhim, Rameen ; Cooper, Lee ; Akbani, Rehan ; Wrensch, Margaret ; Haussler, David ; Aldape, Kenneth D. ; Laird, Peter W. ; Gutmann, David H. ; Noushmehr, Houtan ; Arachchi, Harindra ; Auman, J. Todd ; Balasundaram, Miruna ; Balu, Saianand ; Barnett, Gene ; Baylin, Stephen ; Bell, Sue ; Benz, Christopher ; Bir, Natalie ; Black, Keith L. ; Bodenheimer, Tom ; Boice, Lori ; Bootwalla, Moiz S. ; Bowen, Jay ; Bristow, Christopher A. ; Butterfield, Yaron S.N. ; Chen, Qing Rong ; Chin, Lynda ; Cho, Juok ; Chuah, Eric ; Chudamani, Sudha ; Coetzee, Simon G. ; Cohen, Mark L. ; Colman, Howard ; Couce, Marta ; D'Angelo, Fulvio ; Davidsen, Tanja ; Davis, Amy ; Demchok, John A. ; Devine, Karen ; Ding, Li ; Duell, Rebecca ; Elder, J. Bradley ; Eschbacher, Jennifer M. ; Fehrenbach, Ashley ; Ferguson, Martin ; Frazer, Scott ; Fuller, Gregory ; Fulop, Jordonna ; Gabriel, Stacey B. ; Garofano, Luciano ; Gastier-Foster, Julie M. ; Gehlenborg, Nils ; Gerken, Mark ; Getz, Gad ; Giannini, Caterina ; Gibson, William J. ; Hadjipanayis, Angela ; Hayes, D. Neil ; Heiman, David I. ; Hermes, Beth ; Hilty, Joe ; Hoadley, Katherine A. ; Hoyle, Alan P. ; Huang, Mei ; Jefferys, Stuart R. ; Jones, Corbin D. ; Jones, Steven J.M. ; Ju, Zhenlin ; Kastl, Alison ; Kendler, Ady ; Kim, Jaegil ; Kucherlapati, Raju ; Lai, Phillip H. ; Lawrence, Michael S. ; Lee, Semin ; Leraas, Kristen M. ; Lichtenberg, Tara M. ; Lin, Pei ; Liu, Yuexin ; Liu, Jia ; Ljubimova, Julia Y. ; Lu, Yiling ; Ma, Yussanne ; Maglinte, Dennis T. ; Mahadeshwar, Harshad S. ; Marra, Marco A. ; McGraw, Mary ; McPherson, Christopher ; Meng, Shaowu ; Mieczkowski, Piotr A. ; Miller, C. Ryan ; Mills, Gordon ; Moore, Richard A. ; Mose, Lisle E. ; Mungall, Andrew J. ; Naresh, Rashi ; Naska, Theresa ; Neder, Luciano ; Noble, Michael S. ; Noss, Ardene ; O'Neill, Brian Patrick ; Ostrom, Quinn T. ; Palmer, Cheryl ; Pantazi, Angeliki ; Parfenov, Michael ; Park, Peter J. ; Parker, Joel S. ; Perou, Charles M. ; Pierson, Christopher R. ; Pihl, Todd ; Protopopov, Alexei ; Radenbaugh, Amie ; Ramirez, Nilsa C. ; Rathmell, W. Kimryn ; Ren, Xiaojia ; Roach, Jeffrey ; Robertson, A. Gordon ; Saksena, Gordon ; Schein, Jacqueline E. ; Schumacher, Steven E. ; Seidman, Jonathan ; Senecal, Kelly ; Seth, Sahil ; Shen, Hui ; Shi, Yan ; Shih, Juliann ; Shimmel, Kristen ; Sicotte, Hugues ; Sifri, Suzanne ; Silva, Tiago ; Simons, Janae V. ; Singh, Rosy ; Skelly, Tara ; Sloan, Andrew E. ; Sofia, Heidi J. ; Soloway, Matthew G. ; Song, Xingzhi ; Sougnez, Carrie ; Souza, Camila ; Staugaitis, Susan M. ; Sun, Huandong ; Sun, Charlie ; Tan, Donghui ; Tang, Jiabin ; Tang, Yufang ; Thorne, Leigh ; Trevisan, Felipe Amstalden ; Triche, Timothy ; Van Den Berg, David J. ; Veluvolu, Umadevi ; Voet, Doug ; Wan, Yunhu ; Wang, Zhining ; Warnick, Ronald ; Weinstein, John N. ; Weisenberger, Daniel J. ; Wilkerson, Matthew D. ; Williams, Felicia ; Wise, Lisa ; Wolinsky, Yingli ; Wu, Junyuan ; Xu, Andrew W. ; Yang, Lixing ; Yang, Liming ; Zack, Travis I. ; Zenklusen, Jean C. ; Zhang, Jianhua ; Zhang, Wei ; Zhang, Jiashan ; Zmuda, Erik ; Noushmehr, Houtan ; Iavarone, Antonio ; Verhaak, Roel G.W. / Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. In: Cell. 2016 ; Vol. 164, No. 3. pp. 550-563.
@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 Gordon Mills 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.}",
year = "2016",
month = "1",
day = "28",
doi = "10.1016/j.cell.2015.12.028",
language = "English (US)",
volume = "164",
pages = "550--563",
journal = "Cell",
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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.

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AU - Verhaak, Roel G.W.

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

VL - 164

SP - 550

EP - 563

JO - Cell

JF - Cell

SN - 0092-8674

IS - 3

ER -