Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: Implications for classification of gliomas
Christian Hartmann,Christian Hartmann,Bettina Hentschel,Wolfgang Wick,Wolfgang Wick,David Capper,Jörg Felsberg,Matthias Simon,Manfred Westphal,Gabriele Schackert,Richard Meyermann,Torsten Pietsch,Guido Reifenberger,Michael Weller,Markus Loeffler,Andreas von Deimling,Andreas von Deimling +16 more
Reads0
Chats0
TLDR
Evidence is provided that the IDH1 status is more prognostic for overall survival than standard histological criteria that differentiate high-grade astrocytomas and that much of the prognostic significance of patient age is due to the predominant occurrence of IDH 1 mutations in younger patients.Abstract:
WHO grading of human brain tumors extends beyond a strictly histological grading system by providing a basis predictive for the clinical behavior of the respective neoplasm. For example, patients with glioblastoma WHO grade IV usually show a less favorable clinical course and receive more aggressive first-line treatment than patients with anaplastic astrocytoma WHO grade III. Here we provide evidence that the IDH1 status is more prognostic for overall survival than standard histological criteria that differentiate high-grade astrocytomas. We sequenced the isocitrate dehydrogenase 1 gene (IDH1) at codon 132 in 382 patients with anaplastic astrocytoma and glioblastoma from the NOA-04 trial and from a prospective translational cohort study of the German Glioma Network. Patients with anaplastic astrocytomas carried IDH1 mutations in 60%, and patients with glioblastomas in 7.2%. IDH1 was the most prominent single prognostic factor (RR 2.7; 95% CI 1.6–4.5) followed by age, diagnosis and MGMT. The sequence from more favorable to poorer outcome was (1) anaplastic astrocytoma with IDH1 mutation, (2) glioblastoma with IDH1 mutation, (3) anaplastic astrocytoma without IDH1 mutation and (4) glioblastoma without IDH1 mutation (p < 0.0001). In this combined set of anaplastic astrocytomas and glioblastomas both, IDH1 mutation and IDH1 expression status were of greater prognostic relevance than histological diagnosis according to the current WHO classification system. Our data indicate that much of the prognostic significance of patient age is due to the predominant occurrence of IDH1 mutations in younger patients. Immunohistochemistry using a mutation-specific antibody recognizing the R132H mutation yielded similar results. We propose to complement the current WHO classification and grading of high-grade astrocytic gliomas by the IDH1 mutation status and to use this combined histological and molecular classification in future clinical trials.read more
Citations
More filters
Journal ArticleDOI
The epidemiology of glioma in adults: a "state of the science" review.
Quinn T. Ostrom,Luc Bauchet,Faith G. Davis,Isabelle Deltour,James L. Fisher,Chelsea Eastman Langer,Melike Pekmezci,Judith A. Schwartzbaum,Michelle C. Turner,Kyle M. Walsh,Margaret Wrensch,Jill S. Barnholtz-Sloan +11 more
TL;DR: A “state of the science” review of current research into causes and risk factors for gliomas in adults is provided.
Journal ArticleDOI
Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial
Wolfgang Wick,Michael Platten,Christoph Meisner,Joerg Felsberg,Ghazaleh Tabatabai,Ghazaleh Tabatabai,Matthias Simon,Guido Nikkhah,Kirsten Papsdorf,Joachim P. Steinbach,Joachim P. Steinbach,Michael Sabel,Stephanie E. Combs,Jan Vesper,Jan Vesper,Christian Braun,J. Meixensberger,Ralf Ketter,Regine Mayer-Steinacker,Guido Reifenberger,Michael Weller,Michael Weller +21 more
TL;DR: Temozolomide alone is non-inferior to radiotherapy alone in the treatment of elderly patients with malignant astrocytoma and MGMT promoter methylation seems to be a useful biomarker for outcomes by treatment and could aid decision-making.
Journal ArticleDOI
Epidemiologic and Molecular Prognostic Review of Glioblastoma
Jigisha P. Thakkar,Therese A. Dolecek,Craig Horbinski,Quinn T. Ostrom,Donita Lightner,Jill S. Barnholtz-Sloan,John L. Villano +6 more
TL;DR: The current epidemiology of GBM is reported with new data from the Central Brain Tumor Registry of the United States 2006 to 2010 as well as demonstrate and discuss trends in incidence and survival.
Journal ArticleDOI
Primary brain tumours in adults.
TL;DR: Progress in genomics has defined a new era in neuro-oncology and holds promise for diagntic and therapeutic improvement, and combination therapies seem to be required to achieve a broad and durable antitumour response.
Journal ArticleDOI
Mutational landscape and clonal architecture in grade II and III gliomas
Hiromichi Suzuki,Kosuke Aoki,Kenichi Chiba,Yusuke Sato,Yusuke Shiozawa,Yuichi Shiraishi,Teppei Shimamura,Atsushi Niida,Kazuya Motomura,Fumiharu Ohka,Takashi Yamamoto,Kuniaki Tanahashi,Melissa Ranjit,Toshihiko Wakabayashi,Tetsuichi Yoshizato,Keisuke Kataoka,Kenichi Yoshida,Yasunobu Nagata,Aiko Sato-Otsubo,Hiroko Tanaka,Masashi Sanada,Yutaka Kondo,Hideo Nakamura,Masahiro Mizoguchi,Tatsuya Abe,Yoshihiro Muragaki,Reiko Watanabe,Ichiro Ito,Satoru Miyano,Atsushi Natsume,Seishi Ogawa +30 more
TL;DR: In this article, the authors delineate the entire picture of genetic alterations and affected pathways in these glioma types, with sensitive detection of driver genes Grade II and III gliomas comprise three distinct subtypes characterized by discrete sets of mutations and distinct clinical behaviors, suggesting that there is functional interplay between the mutations that drive clonal selection.
References
More filters
Journal ArticleDOI
The 2007 WHO Classification of Tumours of the Central Nervous System
David N. Louis,Hiroko Ohgaki,Otmar D. Wiestler,Webster K. Cavenee,Peter C. Burger,Anne Jouvet,Bernd W. Scheithauer,Paul Kleihues +7 more
TL;DR: The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneurs tumour of the fourth ventricle, Papillary tumourof the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis.
Journal ArticleDOI
MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma
Monika E. Hegi,Annie-Claire Diserens,Thierry Gorlia,Marie-France Hamou,Nicolas de Tribolet,Nicolas de Tribolet,Michael Weller,Johan M. Kros,Johannes A. Hainfellner,Warren P. Mason,Luigi Mariani,Jacoline E C Bromberg,Peter Hau,René O. Mirimanoff,J. Gregory Cairncross,Robert C. Janzer,Roger Stupp +16 more
TL;DR: Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylation of theMGMT promoter did notHave such a benefit and were assigned to only radiotherapy.
Journal ArticleDOI
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
D. Williams Parsons,Siân Jones,Xiaosong Zhang,Jimmy Lin,Rebecca J. Leary,Philipp Angenendt,Parminder Mankoo,Hannah Carter,I-Mei Siu,Gary L. Gallia,Alessandro Olivi,Roger E. McLendon,B.K. Ahmed Rasheed,Stephen T. Keir,Tatiana Nikolskaya,Yuri Nikolsky,Dana A. Busam,Hanna Tekleab,Luis A. Diaz,James Hartigan,Doug R. Smith,Robert L. Strausberg,Suely Kazue Nagahashi Marie,Sueli Mieko Oba Shinjo,Hai Yan,Gregory J. Riggins,Darell D. Bigner,Rachel Karchin,Nick Papadopoulos,Giovanni Parmigiani,Bert Vogelstein,Victor E. Velculescu,Kenneth W. Kinzler +32 more
TL;DR: Recurrent mutations in the active site of isocitrate dehydrogenase 1 (IDH1) occurred in a large fraction of young patients and in most patients with secondary GBMs and were associated with an increase in overall survival.
Journal ArticleDOI
IDH1 and IDH2 Mutations in Gliomas
Hai Yan,D. Williams Parsons,Genglin Jin,Roger E. McLendon,B.K. Ahmed Rasheed,Weishi Yuan,Ivan Kos,Ines Batinic-Haberle,Siân Jones,Gregory J. Riggins,Henry S. Friedman,Allan H. Friedman,David A. Reardon,James E. Herndon,Kenneth W. Kinzler,Victor E. Velculescu,Bert Vogelstein,Darell D. Bigner +17 more
TL;DR: Mutations of NADP(+)-dependent isocitrate dehydrogenases encoded by IDH1 and IDH2 occur in a majority of several types of malignant gliomas.
Related Papers (5)
IDH1 and IDH2 Mutations in Gliomas
Hai Yan,D. Williams Parsons,Genglin Jin,Roger E. McLendon,B.K. Ahmed Rasheed,Weishi Yuan,Ivan Kos,Ines Batinic-Haberle,Siân Jones,Gregory J. Riggins,Henry S. Friedman,Allan H. Friedman,David A. Reardon,James E. Herndon,Kenneth W. Kinzler,Victor E. Velculescu,Bert Vogelstein,Darell D. Bigner +17 more
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
D. Williams Parsons,Siân Jones,Xiaosong Zhang,Jimmy Lin,Rebecca J. Leary,Philipp Angenendt,Parminder Mankoo,Hannah Carter,I-Mei Siu,Gary L. Gallia,Alessandro Olivi,Roger E. McLendon,B.K. Ahmed Rasheed,Stephen T. Keir,Tatiana Nikolskaya,Yuri Nikolsky,Dana A. Busam,Hanna Tekleab,Luis A. Diaz,James Hartigan,Doug R. Smith,Robert L. Strausberg,Suely Kazue Nagahashi Marie,Sueli Mieko Oba Shinjo,Hai Yan,Gregory J. Riggins,Darell D. Bigner,Rachel Karchin,Nick Papadopoulos,Giovanni Parmigiani,Bert Vogelstein,Victor E. Velculescu,Kenneth W. Kinzler +32 more
MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma
Monika E. Hegi,Annie-Claire Diserens,Thierry Gorlia,Marie-France Hamou,Nicolas de Tribolet,Nicolas de Tribolet,Michael Weller,Johan M. Kros,Johannes A. Hainfellner,Warren P. Mason,Luigi Mariani,Jacoline E C Bromberg,Peter Hau,René O. Mirimanoff,J. Gregory Cairncross,Robert C. Janzer,Roger Stupp +16 more
Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Roger Stupp,Warren P. Mason,Martin J. van den Bent,Michael Weller,Barbara Fisher,Martin J.B. Taphoorn,Karl Belanger,Alba A. Brandes,Christine Marosi,Ulrich Bogdahn,Jürgen Curschmann,Robert C. Janzer,Samuel K. Ludwin,Thierry Gorlia,Anouk Allgeier,Denis Lacombe,J. Gregory Cairncross,Elizabeth Eisenhauer,René O. Mirimanoff +18 more