Recent advances in the molecular understanding of glioblastoma

被引:381
作者
Bleeker, Fonnet E. [1 ]
Molenaar, Remco J. [2 ]
Leenstra, Sieger [3 ,4 ]
机构
[1] Locat AMC, Dept Neurosurg, Neurosurg Ctr Amsterdam, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Dept Cell Biol & Histol, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands
[3] Erasmus MC, Dept Neurosurg, NL-3015 CE Rotterdam, Netherlands
[4] St Elizabeth Hosp, Dept Neurosurg, NL-5022 GC Tilburg, Netherlands
关键词
Glioblastoma; Molecular; (Epi)genetic; Transcriptional; Proteomic; PHASE-II TRIAL; GROWTH-FACTOR RECEPTOR; NEWLY-DIAGNOSED GLIOBLASTOMA; HIGH-GRADE GLIOMA; COMPARATIVE GENOMIC HYBRIDIZATION; CODON; 132; MUTATION; GENE-EXPRESSION; PROMOTER METHYLATION; IDH1; MUTATIONS; COPY NUMBER;
D O I
10.1007/s11060-011-0793-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Glioblastoma is the most common and most aggressive primary brain tumor. Despite maximum treatment, patients only have a median survival time of 15 months, because of the tumor's resistance to current therapeutic approaches. Thus far, methylation of the O (6)-methylguanine-DNA methyltransferase (MGMT) promoter has been the only confirmed molecular predictive factor in glioblastoma. Novel "genome-wide" techniques have identified additional important molecular alterations as mutations in isocitrate dehydrogenase 1 (IDH1) and its prognostic importance. This review summarizes findings and techniques of genetic, epigenetic, transcriptional, and proteomic studies of glioblastoma. It provides the clinician with an up-to-date overview of current identified molecular alterations that should ultimately lead to new therapeutic targets and more individualized treatment approaches in glioblastoma.
引用
收藏
页码:11 / 27
页数:17
相关论文
共 126 条
[1]   Potential role of miRNAs and their inhibitors in glioma treatment [J].
Asadi-Moghaddam, Kaveh ;
Chiocca, E. Antonio ;
Lawler, Sean E. .
EXPERT REVIEW OF ANTICANCER THERAPY, 2010, 10 (11) :1753-1762
[2]   Analysis of the IDH1 codon 132 mutation in brain tumors [J].
Balss, Joerg ;
Meyer, Jochen ;
Mueller, Wolf ;
Korshunov, Andrey ;
Hartmann, Christian ;
von Deimling, Andreas .
ACTA NEUROPATHOLOGICA, 2008, 116 (06) :597-602
[3]   Assessing the significance of chromosomal aberrations in cancer: Methodology and application to glioma [J].
Beroukhim, Rameen ;
Getz, Gad ;
Nghiemphu, Leia ;
Barretina, Jordi ;
Hsueh, Teli ;
Linhart, David ;
Vivanco, Igor ;
Lee, Jeffrey C. ;
Huang, Julie H. ;
Alexander, Sethu ;
Du, Jinyan ;
Kau, Tweeny ;
Thomas, Roman K. ;
Shah, Kinial ;
Soto, Horacio ;
Perner, Sven ;
Prensner, John ;
Debiasi, Ralph M. ;
Demichelis, Francesca ;
Hatton, Charlie ;
Rubin, Mark A. ;
Garraway, Levi A. ;
Nelson, Stan F. ;
Liau, Linda ;
Mischel, Paul S. ;
Cloughesy, Tim F. ;
Meyerson, Matthew ;
Golub, Todd A. ;
Lander, Eric S. ;
Mellinghoff, Ingo K. ;
Sellers, William R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (50) :20007-20012
[4]   Mutations in CIC and FUBP1 Contribute to Human Oligodendroglioma [J].
Bettegowda, Chetan ;
Agrawal, Nishant ;
Jiao, Yuchen ;
Sausen, Mark ;
Wood, Laura D. ;
Hruban, Ralph H. ;
Rodriguez, Fausto J. ;
Cahill, Daniel P. ;
McLendon, Roger ;
Riggins, Gregory ;
Velculescu, Victor E. ;
Oba-Shinjo, Sueli Mieko ;
Marie, Suely Kazue Nagahashi ;
Vogelstein, Bert ;
Bigner, Darell ;
Yan, Hai ;
Papadopoulos, Nickolas ;
Kinzler, Kenneth W. .
SCIENCE, 2011, 333 (6048) :1453-1455
[5]   DNA CONTENT AND CHROMOSOMAL COMPOSITION OF MALIGNANT HUMAN GLIOMAS [J].
BIGNER, SH ;
BJERKVIG, R ;
LAERUM, OD .
NEUROLOGIC CLINICS, 1985, 3 (04) :769-784
[6]   The prognostic IDH1 R132 mutation is associated with reduced NADP+-dependent IDH activity in glioblastoma [J].
Bleeker, Fonnet E. ;
Atai, Nadia A. ;
Lamba, Simona ;
Jonker, Ard ;
Rijkeboer, Denise ;
Bosch, Klazien S. ;
Tigchelaar, Wikky ;
Troost, Dirk ;
Vandertop, W. Peter ;
Bardelli, Alberto ;
Van Noorden, Cornelis J. F. .
ACTA NEUROPATHOLOGICA, 2010, 119 (04) :487-494
[7]   IDH1 Mutations at Residue p.R132 (IDH1R132) Occur Frequently in High-Grade Gliomas But Not in Other Solid Tumors [J].
Bleeker, Fonnet E. ;
Lamba, Simona ;
Leenstra, Sieger ;
Troost, Dirk ;
Hulsebos, Theo ;
Vandertop, W. Peter ;
Frattini, Milo ;
Molinari, Francesca ;
Knowles, Margaret ;
Cerrato, Aniello ;
Rodolfo, Monica ;
Scarpa, Aldo ;
Felicioni, Lara ;
Buttitta, Fiamma ;
Malatesta, Sara ;
Marchetti, Antonio ;
Bardelli, Alberto .
HUMAN MUTATION, 2009, 30 (01) :7-11
[8]   Levetiracetam enhances p53-mediated MGMT inhibition and sensitizes glioblastoma cells to temozolomide [J].
Bobustuc, George C. ;
Baker, Cheryl H. ;
Limaye, Arati ;
Jenkins, Wayne D. ;
Pearl, Gary ;
Avgeropoulos, Nicholas G. ;
Konduri, Santhi D. .
NEURO-ONCOLOGY, 2010, 12 (09) :917-927
[9]   MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients [J].
Brandes, Alba A. ;
Franceschi, Enrico ;
Tosoni, Alicia ;
Blatt, Valeria ;
Pession, Annalisa ;
Tallini, Giovanni ;
Bertorelle, Roberta ;
Bartolini, Stefania ;
Calbucci, Fabio ;
Andreoli, Alvaro ;
Frezza, Giampiero ;
Leonardi, Marco ;
Spagnolli, Federica ;
Ermani, Mario .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (13) :2192-2197
[10]   Recurrence Pattern After Temozolomide Concomitant With and Adjuvant to Radiotherapy in Newly Diagnosed Patients With Glioblastoma: Correlation With MGMT Promoter Methylation Status [J].
Brandes, Alba A. ;
Tosoni, Alicia ;
Franceschi, Enrico ;
Sotti, Guido ;
Frezza, Giampiero ;
Amista, Pietro ;
Morandi, Luca ;
Spagnolli, Federica ;
Ermani, Mario .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (08) :1275-1279