Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial

Hegi, Monika E.; Janzer, Robert C.; Lambiv, Wanyu L.; Gorlia, Thierry; Kouwenhoven, Mathilde C.M.; Hartmann, Christian; Deimling, Andreas von; Martinet, Danielle; Schmutz, N Besuchet; Diserens, Annie‐Claire; Hamou, Marie‐France; Bady, Pierre; Weller, Michael; Bent, Martin J. van den; Mason, Warren P.; Mirimanoff, René-Olivier; Stupp, Roger; Mokhtari, Karima; Wesseling, Pieter

doi:10.1007/s00401-011-0938-4

Cited by 77 publications

(70 citation statements)

References 40 publications

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“…In GB-O cases, the frequency of LOH 1p was from 12 to 24%, 19q was from 32 to 43%, and combined 1p/19q was from 22 to 28% [39,40]. In the more recent EORTC/NCIC trial study concerning a large group of 360 GB cases, an oligodendroglial component was found in 15% of all cases but co-deletion of 1p/19q was found in only one case [41]. Intriguingly, a more detailed study in GB-O using microdissection of tumor tissues with astrocytic and oligodendroglial components revealed no difference in the pattern of genetic alterations on chromosomes 1p and 19q in the same tumors [21].…”

Section: Discussionmentioning

confidence: 96%

Association of loss of heterozygosity with shorter survival in primary glioblastoma patients

Jesionek-Kupnicka

Szybka²,

Potemski³

et al. 2013

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Loss of heterozygosity (LOH) co-deletion 1p/19q, MGMT promoter methylation and/or IDH1 mutation generally signify a better prognosis for patients with glioma. However, the influence of 1p/19q co-deletion and the LOH on other chromosomes in primary glioblastoma on survival is still debatable. The aim of our study was to identify LOH on chromosomes 1p, 19q, 9p, 10q, 13q, and 17p, and evaluate their impact either alone or 1p/19q co-deletion or by groups of LOH on the overall survival of 42 primary glioblastoma patients without an oligodendroglial component. These patients were additionally molecularly characterized for EGFR amplification, IDH1 mutations and TP53 mutations. We assessed their influence on the overall survival of glioblastoma patients. LOH in at least one of the loci on all examined chromosomes was detected in 65% of cases and was significantly associated with shorter overall survival (hazard ratio 3.07; 95% CI: 1.29-7.31, p = 0.006). 1p/19q co-deletion was infrequent (7.14%) and had no impact on overall survival. Our results indicate that in primary glioblastoma a specific LOH group analysis may be important for the prognosis. LOH 1p/19q co-deletion is rare in glioblastoma without an oligodendroglial component and has no impact on patient survival.

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Section: Discussionmentioning

confidence: 96%

Association of loss of heterozygosity with shorter survival in primary glioblastoma patients

Jesionek-Kupnicka

Szybka²,

Potemski³

et al. 2013

pjp

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“…Tumors caused by a mutation in the IDH gene encompass a spectrum from astrocytomas to oligodendrogliomas (41). At the same time, there is increasing evidence that a morphologic subclassification of gliomas lacks clinical or prognostic relevance (42), and there is growing support for an approach combining morphologic assessment and molecular profiling of gliomas (31).…”

Section: Discussionmentioning

confidence: 99%

Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor PropagationIn Vitro

et al. 2013

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Brain tumors are thought to originate from stem/progenitor cell populations that acquire specific genetic mutations. Although current preclinical models have relevance to human pathogenesis, most do not recapitulate the histogenesis of the human disease. Recently, a large series of human gliomas and medulloblastomas were analyzed for genetic signatures of prognosis and therapeutic response. Using a mouse model system that generates three distinct types of intrinsic brain tumors, we correlated RNA and protein expression levels with human brain tumors. A combination of genetic mutations and cellular environment during tumor propagation defined the incidence and phenotype of intrinsic murine tumors. Importantly, in vitro passage of cancer stem cells uniformly promoted a glial expression profile in culture and in brain tumors. Gene expression profiling revealed that experimental gliomas corresponded to distinct subclasses of human glioblastoma, whereas experimental supratentorial primitive neuroectodermal tumors (sPNET) correspond to atypical teratoid/ rhabdoid tumor (AT/RT), a rare childhood tumor. Cancer Res; 73(18); 5834-44. Ó2013 AACR.

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“…16 Furthermore, a recent study reported that glioblastomas carrying IDH1 mutations are associated with a better survival than anaplastic astrocytomas without these mutations. 17 Whether the recognition of an oligodendroglial component in glioblastomas has prognostic value is still under debate [18][19][20] and also within this glioblastoma subtype a different origin of this oligodendroglial component is hypothesized. 19 An age-dependent correlation-which was found for the prognostic effect of molecular markers like TP53, 1p loss and CDKN2A-may well contribute to the inconsistencies between studies on the prognostic relevance of specific molecular markers.…”

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confidence: 99%

Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution

et al. 2013

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The histopathological diagnosis of diffuse gliomas often lacks the precision that is needed for tailored treatment of individual patients. Assessment of the molecular aberrations will probably allow more robust and prognostically relevant classification of these tumors. Markers that have gained a lot of interest in this respect are co-deletion of complete chromosome arms 1p and 19q, (hyper)methylation of the MGMT promoter and IDH1 mutations. The aim of this study was to assess the prognostic significance of complete 1p/19q co-deletion, MGMT promoter methylation and IDH1 mutations in patients suffering from diffuse gliomas. The presence of these molecular aberrations was investigated in a series of 561 diffuse astrocytic and oligodendroglial tumors (low grade n ¼ 110, anaplastic n ¼ 118 and glioblastoma n ¼ 333) and correlated with age at diagnosis and overall survival. Complete 1p/19q co-deletion, MGMT promoter methylation and/or IDH1 mutation generally signified a better prognosis for patients with a diffuse glioma including glioblastoma. However, in all 10 patients with a histopathological diagnosis of glioblastoma included in this study complete 1p/19q co-deletion was not associated with improved survival. Furthermore, in glioblastoma patients 450 years of age the favorable prognostic significance of IDH1 mutation and MGMT promoter methylation was absent. In conclusion, molecular diagnostics is a powerful tool to obtain prognostically relevant information for glioma patients. However, for individual patients the molecular information should be interpreted with caution and weighed in the context of parameters such as age and histopathological diagnosis. Modern Pathology (2013) 26, 922-929;

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Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial

Cited by 77 publications

References 40 publications

Association of loss of heterozygosity with shorter survival in primary glioblastoma patients

Association of loss of heterozygosity with shorter survival in primary glioblastoma patients

Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor PropagationIn Vitro

Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution

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