Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors
Jeanette E. Eckel-Passow,Daniel H. Lachance,Annette M. Molinaro,Kyle M. Walsh,Paul A. Decker,Hugues Sicotte,Melike Pekmezci,Terri Rice,Matt L. Kosel,Ivan Smirnov,Gobinda Sarkar,Alissa Caron,Thomas M. Kollmeyer,Corinne Praska,Anisha R. Chada,Chandralekha Halder,Helen M. Hansen,Lucie McCoy,Paige M. Bracci,Roxanne Marshall,Shichun Zheng,Gerald F. Reis,Alexander R. Pico,Brian P. O'Neill,Jan C. Buckner,Caterina Giannini,Jason T. Huse,Arie Perry,Tarik Tihan,Mitchell S. Berger,Susan M. Chang,Michael D. Prados,Joseph L. Wiemels,John K. Wiencke,Margaret Wrensch,Robert B. Jenkins +35 more
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TLDR
The five glioma molecular groups had different ages at onset, overall survival, and associations with germline variants, which implies that they are characterized by distinct mechanisms of pathogenesis.Abstract:
BACKGROUND The prediction of clinical behavior, response to therapy, and outcome of infiltrative glioma is challenging. On the basis of previous studies of tumor biology, we defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). We tested the hypothesis that within groups based on these features, tumors would have similar clinical variables, acquired somatic alterations, and germline variants. METHODS We scored tumors as negative or positive for each of these markers in 1087 gliomas and compared acquired alterations and patient characteristics among the five primary molecular groups. Using 11,590 controls, we assessed associations between these groups and known glioma germline variants.read more
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The somatic genomic landscape of glioblastoma
Cameron Brennan,Roel G.W. Verhaak,Aaron McKenna,Benito Campos,Houtan Noushmehr,Sofie R. Salama,Siyuan Zheng,Debyani Chakravarty,J. Zachary Sanborn,Samuel H. Berman,Rameen Beroukhim,Brady Bernard,Chang-Jiun Wu,Giannicola Genovese,Ilya Shmulevich,Jill S. Barnholtz-Sloan,Lihua Zou,Rahulsimham Vegesna,Sachet A. Shukla,Giovanni Ciriello,W. K. Yung,Wei Zhang,Carrie Sougnez,Tom Mikkelsen,Kenneth Aldape,Darell D. Bigner,Erwin G. Van Meir,Michael D. Prados,Andrew E. Sloan,Keith L. Black,Jennifer M. Eschbacher,Gaetano Finocchiaro,William A. Friedman,David W. Andrews,Abhijit Guha,Mary Iacocca,Brian P. O'Neil,Greg Foltz,Jerome Myers,Daniel J. Weisenberger,Robert Penny,Raju Kucherlapati,Charles M. Perou,D. Neil Hayes,Richard A. Gibbs,Marco A. Marra,Gordon B. Mills,Eric S. Lander,Paul T. Spellman,Richard K. Wilson,Chris Sander,John N. Weinstein,Matthew Meyerson,Stacey Gabriel,Peter W. Laird,David Haussler,Gad Getz,Lynda Chin +57 more
TL;DR: In this article, the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs) was described, including several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA.
Journal ArticleDOI
Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.
Daniel J. Brat,Roel G.W. Verhaak,Kenneth Aldape,W. K. Alfred Yung,Sofie R. Salama,Lee Cooper,Esther Rheinbay,C. Ryan Miller,Mark Vitucci,Olena Morozova,A. Gordon Robertson,Houtan Noushmehr,Peter W. Laird,Andrew D. Cherniack,Rehan Akbani,Jason T. Huse,Giovanni Ciriello,Laila M. Poisson,Jill S. Barnholtz-Sloan,Mitchel S. Berger,Cameron Brennan,Rivka R. Colen,Howard Colman,Adam E. Flanders,Caterina Giannini,Mia Grifford,Antonio Iavarone,Rajan Jain,Isaac Joseph,Jaegil Kim,Katayoon Kasaian,Tom Mikkelsen,Bradley A. Murray,Brian P. O'Neill,Lior Pachter,Donald W. Parsons,Carrie Sougnez,Erik P. Sulman,Scott R. VandenBerg,Erwin G. Van Meir,Andreas von Deimling,Hailei Zhang,Daniel Crain,Kevin Lau,David Mallery,Scott Morris,Joseph Paulauskis,Robert Penny,Troy Shelton,Mark E. Sherman,Peggy Yena,Aaron D. Black,Jay Bowen,Katie Dicostanzo,Julie M. Gastier-Foster,Kristen M. Leraas,Tara M. Lichtenberg,Christopher R. Pierson,Nilsa C. Ramirez,Cynthia Taylor,Stephanie Weaver,Lisa Wise,Erik Zmuda,Tanja M. Davidsen,John A. Demchok,Greg Eley,Martin L. Ferguson,Carolyn M. Hutter,Kenna R. Mills Shaw,Bradley A. Ozenberger,Margi Sheth,Heidi J. Sofia,Roy Tarnuzzer,Zhining Wang,Liming Yang,Jean C. Zenklusen,Brenda Ayala,Julien Baboud,Sudha Chudamani,Mark A. Jensen,Jia Liu,Todd Pihl,Rohini Raman,Yunhu Wan,Ye Wu,Adrian Ally,J. Todd Auman,Miruna Balasundaram,Saianand Balu,Stephen B. Baylin,Rameen Beroukhim,Moiz S. Bootwalla,Reanne Bowlby,Christopher A. Bristow,Denise Brooks,Yaron S.N. Butterfield,Rebecca Carlsen,Scott L. Carter,Lynda Chin,Andy Chu,Eric Chuah,Kristian Cibulskis,Amanda Clarke,Simon G. Coetzee,Noreen Dhalla,Timothy R. Fennell,Sheila A. Fisher,Stacey Gabriel,Gad Getz,Richard A. Gibbs,Ranabir Guin,Angela Hadjipanayis,D. Neil Hayes,Toshinori Hinoue,Katherine A. Hoadley,Robert A. Holt,Alan P. Hoyle,Stuart R. Jefferys,Steven J.M. Jones,Corbin D. Jones,Raju Kucherlapati,Phillip H. Lai,Eric S. Lander,Semin Lee,Lee Lichtenstein,Yussanne Ma,Dennis T. Maglinte,Harshad S. Mahadeshwar,Marco A. Marra,Michael Mayo,Shaowu Meng,Matthew Meyerson,Piotr A. Mieczkowski,Richard A. Moore,Lisle E. Mose,Andrew J. Mungall,Angeliki Pantazi,Michael Parfenov,Peter J. Park,Joel S. Parker,Charles M. Perou,Alexei Protopopov,Xiaojia Ren,Jeffrey Roach,Thais S. Sabedot,Jacqueline E. Schein,Steven E. Schumacher,Jonathan G. Seidman,Sahil Seth,Hui Shen,Janae V. Simons,Payal Sipahimalani,Matthew G. Soloway,Xingzhi Song,Huandong Sun,Barbara Tabak,Angela Tam,Donghui Tan,Jiabin Tang,Nina Thiessen,Timothy J. Triche,David Van Den Berg,Umadevi Veluvolu,Scot Waring,Daniel J. Weisenberger,Matthew D. Wilkerson,Tina Wong,Junyuan Wu,Liu Xi,Andrew Wei Xu,Lixing Yang,Travis I. Zack,Jianhua Zhang,B. Arman Aksoy,Harindra Arachchi,Chris Benz,Brady Bernard,Daniel E. Carlin,Juok Cho,Daniel DiCara,Scott Frazer,Gregory N. Fuller,Jianjiong Gao,Nils Gehlenborg,David Haussler,David I. Heiman,Lisa Iype,Anders Jacobsen,Zhenlin Ju,Sol Katzman,Hoon Kim,Theo A. Knijnenburg,Richard Kreisberg,Michael S. Lawrence,William M. Lee,Kalle Leinonen,Pei Lin,Shiyun Ling,Wen-Bin Liu,Yingchun Liu,Yuexin Liu,Yiling Lu,Gordon B. Mills,Sam Ng,Michael S. Noble,Evan O. Paull,Arvind Rao,Sheila Reynolds,Gordon Saksena,Zack Sanborn,Chris Sander,Nikolaus Schultz,Yasin Senbabaoglu,Ronglai Shen,Ilya Shmulevich,Rileen Sinha,Josh Stuart,S. Onur Sumer,Yichao Sun,Natalie Tasman,Barry S. Taylor,Doug Voet,Nils Weinhold,John N. Weinstein,Da Yang,Kosuke Yoshihara,Siyuan Zheng,Wei Zhang,Lihua Zou,Ty Abel,Sara Sadeghi,Mark L. Cohen,Jenny Eschbacher,Eyas M. Hattab,Aditya Raghunathan,Matthew Schniederjan,Dina Aziz,Gene Barnett,Wendi Barrett,Darell D. Bigner,Lori Boice,Cathy Brewer,Chiara Calatozzolo,Benito Campos,Carlos Gilberto Carlotti,Timothy A. Chan,Lucia Cuppini,Erin Curley,Stefania Cuzzubbo,Karen Devine,Francesco DiMeco,Rebecca Duell,J. Bradley Elder,Ashley Fehrenbach,Gaetano Finocchiaro,William A. Friedman,Jordonna Fulop,Johanna Gardner,Beth Hermes,Christel Herold-Mende,Christine Jungk,Ady Kendler,Norman L. Lehman,Eric S. Lipp,Ouida Liu,Randy Mandt,Mary McGraw,Roger E. McLendon,Christopher M. McPherson,Luciano Neder,Phuong L. Nguyen,Ardene Noss,Raffaele Nunziata,Quinn T. Ostrom,Cheryl A. Palmer,Alessandro Perin,Bianca Pollo,Alexander Potapov,Olga Potapova,W. Kimryn Rathmell,D L Rotin,Lisa Scarpace,Cathy Schilero,Kelly Senecal,Kristen Shimmel,Vsevolod Shurkhay,Suzanne Sifri,Rosy Singh,Andrew E. Sloan,Kathy Smolenski,Susan M. Staugaitis,Ruth Steele,Leigh B. Thorne,Daniela Pretti da Cunha Tirapelli,Andreas Unterberg,Mahitha Vallurupalli,Yun Wang,Ronald E. Warnick,Felicia Williams,Yingli Wolinsky,Sue E. Bell,Mara Rosenberg,Chip Stewart,Franklin W. Huang,Jonna Grimsby,Amie Radenbaugh,Jianan Zhang +306 more
TL;DR: The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class.
Journal ArticleDOI
Dynamic RNA Modifications in Gene Expression Regulation
TL;DR: Roles for mRNA modification in nearly every aspect of the mRNA life cycle, as well as in various cellular, developmental, and disease processes are revealed.
Journal ArticleDOI
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 Maria Pagnotta,Samreen Anjum,Jiguang Wang,Ganiraju C. Manyam,Pietro Zoppoli,Shiyun Ling,Arjun A. Rao,Mia Grifford,Andrew D. Cherniack,Hailei Zhang,Laila M. Poisson,Carlos Gilberto Carlotti,Daniela Pretti da Cunha Tirapelli,Arvind Rao,Tom Mikkelsen,Ching C. Lau,W. K. Alfred Yung,Raul Rabadan,Jason T. Huse,Daniel J. Brat,Norman L. Lehman,Jill S. Barnholtz-Sloan,Siyuan Zheng,Kenneth R. Hess,Ganesh Rao,Matthew Meyerson,Rameen Beroukhim,Lee Cooper,Rehan Akbani,Margaret Wrensch,David Haussler,Kenneth Aldape,Peter W. Laird,David H. Gutmann,Houtan Noushmehr,Antonio Iavarone,Roel G.W. Verhaak +45 more
TL;DR: The complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas were defined from The Cancer Genome Atlas and molecular profiles were used to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease.
Journal ArticleDOI
Management of glioblastoma: State of the art and future directions.
Aaron C. Tan,David M. Ashley,Giselle Y. Lopez,Michael D. Malinzak,Henry S. Friedman,Mustafa Khasraw +5 more
TL;DR: Supportive and palliative care remain important considerations throughout the disease course in the multimodality approach to management, and innovative clinical trial designs with biomarker-enrichment strategies are needed to ultimately improve the outcome of patients with glioblastoma.
References
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Journal ArticleDOI
Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1
Roel G.W. Verhaak,Katherine A. Hoadley,Elizabeth Purdom,Victoria Wang,Yuan-yuan Qi,Matthew D. Wilkerson,C. Ryan Miller,Li Ding,Todd R. Golub,Jill P. Mesirov,Gabriele Alexe,Michael S. Lawrence,Michael O'Kelly,Pablo Tamayo,Barbara A. Weir,Stacey Gabriel,Wendy Winckler,Supriya Gupta,Lakshmi Jakkula,Heidi S. Feiler,J. Graeme Hodgson,C. David James,Jann N. Sarkaria,Cameron Brennan,Ari B. Kahn,Paul T. Spellman,Richard K. Wilson,Terence P. Speed,Terence P. Speed,Joe W. Gray,Matthew Meyerson,Gad Getz,Charles M. Perou,Charles M. Perou,D. Neil Hayes +34 more
TL;DR: A robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes is described and multidimensional genomic data is integrated to establish patterns of somatic mutations and DNA copy number.
Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1
Roel G.W. Verhaak,Katherine A. Hoadley,Elizabeth Purdom,Victoria Wang,Yuan-yuan Qi,Matthew D. Wilkerson,C. Ryan Miller,Li Ding,Todd R. Golub,Jill P. Mesirov,Gabriele Alexe,Michael S. Lawrence,Michael O'Kelly,Pablo Tamayo,Barbara A. Weir,Stacey Gabriel,Wendy Winckler,Supriya Gupta,Lakshmi Jakkula,Heidi S. Feiler,J. Graeme Hodgson,C. David James,Jann N. Sarkaria,Cameron Brennan,Ari B. Kahn,Paul T. Spellman,Richard K. Wilson,Terence P. Speed,Terence P. Speed,Joe W. Gray,Matthew Meyerson,Gad Getz,Charles M. Perou,Charles M. Perou,D. Neil Hayes +34 more
TL;DR: The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM) and proposed a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes as discussed by the authors.
Journal ArticleDOI
The Somatic Genomic Landscape of Glioblastoma
Cameron Brennan,Roel G.W. Verhaak,Aaron McKenna,Benito Campos,Houtan Noushmehr,Sofie R. Salama,Siyuan Zheng,Debyani Chakravarty,J. Zachary Sanborn,Samuel H. Berman,Rameen Beroukhim,Brady Bernard,Chang-Jiun Wu,Giannicola Genovese,Ilya Shmulevich,Jill S. Barnholtz-Sloan,Lihua Zou,Rahulsimham Vegesna,Sachet A. Shukla,Giovanni Ciriello,W. K. Yung,Wei Zhang,Carrie Sougnez,Tom Mikkelsen,Kenneth Aldape,Darell D. Bigner,Erwin G. Van Meir,Michael D. Prados,Andrew E. Sloan,Keith L. Black,Jennifer M. Eschbacher,Gaetano Finocchiaro,William A. Friedman,David W. Andrews,Abhijit Guha,Mary Iacocca,Brian P. O'Neill,Greg Foltz,Jerome Myers,Daniel J. Weisenberger,Robert Penny,Raju Kucherlapati,Charles M. Perou,D. Neil Hayes,Richard A. Gibbs,Marco A. Marra,Gordon B. Mills,Eric S. Lander,Paul T. Spellman,Richard K. Wilson,Chris Sander,John N. Weinstein,Matthew Meyerson,Stacey Gabriel,Peter W. Laird,David Haussler,Gad Getz,Lynda Chin +57 more
TL;DR: Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM.
Journal ArticleDOI
Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis
Heidi S. Phillips,Samir Kharbanda,Ruihuan Chen,William F. Forrest,Robert Soriano,Thomas D. Wu,Anjan Misra,Janice Nigro,Howard Colman,Liliana Soroceanu,P. Mickey Williams,Zora Modrusan,Burt G. Feuerstein,Kenneth Aldape +13 more
TL;DR: Previously undescribed prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis, suggesting functional relevance of tumor subtype molecular signatures is suggested by the ability of cell line signatures to predict neurosphere growth.
The somatic genomic landscape of glioblastoma
Cameron Brennan,Roel G.W. Verhaak,Aaron McKenna,Benito Campos,Houtan Noushmehr,Sofie R. Salama,Siyuan Zheng,Debyani Chakravarty,J. Zachary Sanborn,Samuel H. Berman,Rameen Beroukhim,Brady Bernard,Chang-Jiun Wu,Giannicola Genovese,Ilya Shmulevich,Jill S. Barnholtz-Sloan,Lihua Zou,Rahulsimham Vegesna,Sachet A. Shukla,Giovanni Ciriello,W. K. Yung,Wei Zhang,Carrie Sougnez,Tom Mikkelsen,Kenneth Aldape,Darell D. Bigner,Erwin G. Van Meir,Michael D. Prados,Andrew E. Sloan,Keith L. Black,Jennifer M. Eschbacher,Gaetano Finocchiaro,William A. Friedman,David W. Andrews,Abhijit Guha,Mary Iacocca,Brian P. O'Neil,Greg Foltz,Jerome Myers,Daniel J. Weisenberger,Robert Penny,Raju Kucherlapati,Charles M. Perou,D. Neil Hayes,Richard A. Gibbs,Marco A. Marra,Gordon B. Mills,Eric S. Lander,Paul T. Spellman,Richard K. Wilson,Chris Sander,John N. Weinstein,Matthew Meyerson,Stacey Gabriel,Peter W. Laird,David Haussler,Gad Getz,Lynda Chin +57 more
TL;DR: In this article, the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs) was described, including several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA.
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