Isocitrate Dehydrogenase 1 Codon 132 Mutation Is an Important Prognostic Biomarker in Gliomas

Sanson, Marc; Marie, Yannick; Paris, Sophie; Idbaïh, Ahmed; Laffaire, Julien; Ducray, François; Hallani, Soufiane El; Boisselier, Blandine; Mokhtari, Karima; Hoang-Xuân, Khê; Delattre, Jean‐Yves

doi:10.1200/jco.2009.21.9832

Cited by 910 publications

(756 citation statements)

References 13 publications

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“…Sanson et al. (2009) analyzed the presence of the mutation of IDH1 R132H based on WHO tumor grading, which was found, from higher to lower frequency, in grade II and grade III astrocytomas and primary GMBs, with similar results found by Ducray and Shibahara groups (Ducray et al., 2011; Shibahara et al., 2011). Our primary tumors cohort presents R132H mutation mainly in grade II group, 86% of heterozygote patients belong to this group, and IDH1 R132H mutation is related to this stage (Table 3).…”

Section: Discussionsupporting

confidence: 71%

“…Regarding the survival analysis, previous studies demonstrated the prognostic significance of IDH1 mutations (Arita et al., 2015; Brennan et al., 2013; Ducray et al., 2011; Hartmann et al., 2010; Killela et al., 2014; Lewandowska et al., 2014; Mellai et al., 2011; Olar et al., 2012; Parsons et al., 2008; Polivka et al., 2014; Sanson et al., 2009; Shibahara et al., 2011; Sun et al., 2013; Takano et al., 2012; Weller et al., 2009). Some authors observed that OS and PFS in IDH mutated cases were about twice longer than in wild‐type patients (Arita et al., 2015; Polivka et al., 2014), and others showed that mutation in IDH1 was an independent factor for a favorable prognosis (Brennan et al., 2013; Ducray et al., 2011; Polivka et al., 2014; Sanson et al., 2009; Shibahara et al., 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Some authors observed that OS and PFS in IDH mutated cases were about twice longer than in wild‐type patients (Arita et al., 2015; Polivka et al., 2014), and others showed that mutation in IDH1 was an independent factor for a favorable prognosis (Brennan et al., 2013; Ducray et al., 2011; Polivka et al., 2014; Sanson et al., 2009; Shibahara et al., 2011). However, this hypothesis was rejected by other groups taking into account other factors such as surgery and radiotherapy‐chemotherapy treatments when evaluating the survival of these patients (Ichimura et al., 2009; Rineer et al., 2010; Thota et al., 2012).…”

Section: Discussionmentioning

confidence: 99%

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Genetic alterations of IDH1 and Vegf in brain tumors

et al. 2017

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BackgroundThis study evaluates the presence of R132H mutation in isocitrate dehydrogenase (IDH1) gene and the vascular endothelial growth factor (VEGF) +936 C/T polymorphism in brain tumors. The impact of these genetic alterations on overall survival (OS) and progression free survival (PFS) was evaluated.MethodsA cohort of 80 patients surgically treated at Hospital Clínico San Carlos, Madrid, between March 2004 and November 2012, was analyzed. Tumors were distributed in 73 primary brain tumors (gliomas, meningiomas, hemangiopericytomas and hemangioblastomas) and seven secondary tumors evolved from a low grade glioma, thus providing a mixed sample.Results IDH1 R132H gene mutation was found in 12 patients (15%) and appears more frequently in secondary tumors (5 (71.4%) whereas in 7 (9.7%) primary tumors (p < .001)). The mutation is related to WHO grade II in primary tumors and a supratentorial location in secondary tumors. The OS analysis for IDH1 showed a tendency towards a better prognosis of the tumors containing the mutation (p = .059).The IDH1 R132H mutation confers a better PFS (p = .025) on primary tumors. The T allele of VEFG +936 C/T polymorphism was found in 16 patients (20%). No relation was found between this polymorphism and primary or secondary tumor, neither with OS or PFS.Conclusions IDH1 R132H gene mutation is exclusive in supratentorial tumors and more frequent in secondary ones, with a greater survival trend and better PFS in patients who carry it. The T allele of VEGF +936 C/T polymorphism is more common in primary tumors, although there is no statistical relation with survival.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genetic alterations of IDH1 and Vegf in brain tumors

et al. 2017

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“…Isocitrate dehydrogenase gene mutations, estimated to occur in 70–90% of diffuse lower grade gliomas, are strongly implicated in both tumourigenesis and prognosis 23, 24, 25. Loss of heterozygosity of 1p19q, was occurred in 60–80% of oligodendroglioma and up to 45% of oligoastrocytoma 26.…”

Section: Discussionmentioning

confidence: 99%

RUNX3 is down‐regulated in glioma by Myc‐regulated miR‐4295

Zheng

Diao

et al. 2016

J Cellular Molecular Medi

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MicroRNAs are increasingly reported as tumour suppressors that regulate gene expression after transcription. Our results demonstrated that miR‐4295 is overexpression in glioma tissues and its level is significantly correlated with clinical stage. We also found that miR‐4295 inhibited the cell G0/G1 arrest and apoptosis leading to promoted cell proliferation and activity. The murine modelling study revealed that female nude mice injected with U87/anti‐miR‐4295 exhibit subcutaneous tumours in the right groin. Compared with anti‐NC, the tumour volume was significantly decreased in anti‐miR‐4295 treatment group. Furthermore, we confirmed miR‐4295 mediates the expression of RUNX3 by targeting its 3′untranslation region. In addition, N‐myc protein also could bind to the promoter of pri‐miR‐4295 and inhibit the expression of RUNX3 in glioma cells. These results validate a pathogenetic role of a miR‐4295 in gliomas and establish a potentially regulatory and signalling pathway involving N‐myc/miR‐4295/RUNX3 in gliomas.

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“…14 Similar results were obtained in the EORTC trial 26951, in that MGMT promoter methylation was prognostic for PFS in both armsradiotherapy alone and radiotherapy followed by PCV. 15 The high correlation of MGMT promoter methylation with the 1p19q co-deletion 15,57,58 and isocitrate dehydrogenase (IDH) gene mutations, 59 which are known to be favorable prognostic factors in anaplastic glioma, 14,60,61 might indicate that epigenetic deregulation of MGMT occurs in a specific pathogenetic context in anaplastic gliomas. Since MGMT promoter methylation is prognostic and not predictive for chemotherapy response in anaplastic gliomas, a methylated MGMT promoter should not be used to justify the upfront treatment of these tumors with temozolomide-based radiochemotherapy in the absence of appropriate data from studies such as CATNON (http://clinicaltrials.gov, NCT00626990).…”

Section: Anaplastic Gliomamentioning

confidence: 99%

MGMT promoter methylation in malignant gliomas: ready for personalized medicine?

et al. 2009

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The DNA repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT) antagonizes the genotoxic effects of alkylating agents. MGMT promoter methylation is the key mechanism of MGMT gene silencing and predicts a favorable outcome in patients with glioblastoma who are exposed to alkylating agent chemotherapy. This biomarker is on the verge of entering clinical decision-making and is currently used to stratify or even select glioblastoma patients for clinical trials. In other subtypes of glioma, such as anaplastic gliomas, the relevance of MGMT promoter methylation might extend beyond the prediction of chemosensitivity, and could reflect a distinct molecular profile.Here, we review the most commonly used assays for evaluation of MGMT status, outline the prerequisites for standardized tests, and evaluate reasons for difficulties in reproducibility. We critically discuss the prognostic and predictive value of MGMT silencing, reviewing trials in which patients with different types of glioma were treated with various chemotherapy schedules, either upfront or at recurrence. Standardization of MGMT testing requires comparison of different technologies across laboratories, and prospectively validated cut-off values for prognostic or predictive effects. Moreover, future clinical trials will need to determine, for each subtype of glioma, the degree to which MGMT promoter methylation is predictive or prognostic, and whether testing should become routine clinical practice.

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Isocitrate Dehydrogenase 1 Codon 132 Mutation Is an Important Prognostic Biomarker in Gliomas

Abstract: This study indicates that IDH1 codon 132 mutation is closely linked to the genomic profile of the tumor and constitutes an important prognostic marker in grade 2 to 4 gliomas.

Cited by 910 publications

References 13 publications

Genetic alterations of IDH1 and Vegf in brain tumors

Genetic alterations of IDH1 and Vegf in brain tumors

RUNX3 is down‐regulated in glioma by Myc‐regulated miR‐4295

MGMT promoter methylation in malignant gliomas: ready for personalized medicine?

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