Relationship between Tumor Enhancement, Edema,<i>IDH1</i>Mutational Status,<i>MGMT</i>Promoter Methylation, and Survival in Glioblastoma

Carrillo, Jose; Lai, Albert; Nghiemphu, Phioanh L.; Kim, H.J.; Phillips, Heidi S.; Kharbanda, Samir; Moftakhar, Parham; Lalaezari, S.; Yong, William H.; Ellingson, Benjamin M.; Cloughesy, Tim; Pope, Whitney B.

doi:10.3174/ajnr.a2950

Cited by 269 publications

(232 citation statements)

References 48 publications

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“…While TP53 mutation status failed to stratify the survival of both PFS and OS. Our result concerning the predictive value of IDH1 and MGMT methylation was in concordance with previous study (Carrillo et al, 2012;Molenaar et al, 2014). Nevertheless, based on the IDH1 wild type status, MGMT promoter methylation could not differentiate the outcome of patients with GBM treated with radiochemotherapy but TP53 mutation status showed predictive effect on the prognostic survival, patients with TP53 mutation experienced a longer PFS and OS than patients without mutated TP53 (p=0.003 for PFS and p=0.029 for OS respectively).…”

Section: Discussionsupporting

confidence: 90%

Prognostic Value of MGMT Promoter Methylation and TP53 Mutation in Glioblastomas Depends on IDH1 Mutation

Wang

Wang²,

Ma³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Asian Pac J Cancer Prev, 15 (24), 10893-10898 IntroductionGlioblastoma multiform (GBM), classified as World Health Organization (WHO) grade IV, is the most common malignant brain tumors in adults with an incidence rate of 23 per 100,000 persons (Stancheva et al., 2014). Their clinical course varies substantially, such that some patients succumb to progressive disease within weeks while others survive for a decade or more. Current treatments include surgery, radiation therapy and chemotherapy (Sathornsumetee et al., 2007;Koca et al., 2014;Pashaki et al., 2014). However, the median survival is still not optimistic. In spite of the existing classification, GBM subgroups are not homogeneous in terms of survival (Molenaar et al., 2014). Several prognostic factors have been established, including age, preoperative Karnofsky Performance Status (KPS), extent of resection, and also some molecular markers.Recently, molecular markers were shown to be helpful in predicting prognosis and treatment response. Three gene markers that have attracted most interest in this respect are mutations in the isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) gene (Stancheva et al., 2014), hypermethylation of the O 6 -methylguanine-DNA methyltransferase (MGMT) promoter, and complete deletion of both 1p and 19q. Abstract Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas.We investigated the prognostic significance of O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy and chemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylation and TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status (KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, those with an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorable outcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas with MGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status.

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Section: Discussionsupporting

confidence: 90%

Prognostic Value of MGMT Promoter Methylation and TP53 Mutation in Glioblastomas Depends on IDH1 Mutation

Wang

Wang²,

Ma³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…Patients with GBM with MGMT promotor methylation are more responsive to temozolomide therapy and have better clinical outcome than those without it. [27][28][29] Therefore, the detection of IDH1 mutations and MGMT promotor methylation is of great importance for patients with GBM. Carrillo et al 29 suggested that patients with mutant IDH1 have low vascular endothelial growth factor levels, which are associated with contrast enhancement.…”

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confidence: 99%

“…[27][28][29] Therefore, the detection of IDH1 mutations and MGMT promotor methylation is of great importance for patients with GBM. Carrillo et al 29 suggested that patients with mutant IDH1 have low vascular endothelial growth factor levels, which are associated with contrast enhancement. These findings led to the hypothesis that measurement of tumor vascularity and the necrosis area would be helpful to differentiate IDH1 mutation status.…”

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confidence: 99%

MR Imaging–Based Analysis of Glioblastoma Multiforme: Estimation ofIDH1Mutation Status

Yamashita¹,

Hiwatashi²,

Togao³

et al. 2015

AJNR Am J Neuroradiol

111

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BACKGROUND AND PURPOSE: Glioblastoma multiforme is highly aggressive and the most common type of primary malignant brain tumor in adults. Imaging biomarkers may provide prognostic information for patients with this condition. Patients with glioma with isocitrate dehydrogenase 1 (IDH1) mutations have a better clinical outcome than those without such mutations. Our purpose was to investigate whether the IDH1 mutation status in glioblastoma multiforme can be predicted by using MR imaging.

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“…IDH1 R132H mutation overexpression has been shown to decrease cell proliferation (Parsons et al., 2008). Several studies show the presence of the IDH1 R132H mutation in 70–90% of secondary GBMs and 10% primary GBMs, both cases associated with young patients and a higher overall survival rate (Bleeker et al., 2012; Carrillo et al., 2012; Mellai et al., 2011; Weller et al., 2009). The median survival of patients with IDH1 mutation is 3.8 years compared with 1.1 years in patients with wild‐type IDH1 (Parsons et al., 2008).…”

Section: Introductionmentioning

confidence: 99%

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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Relationship between Tumor Enhancement, Edema,IDH1Mutational Status,MGMTPromoter Methylation, and Survival in Glioblastoma

Abstract: BACKGROUND AND PURPOSE:Both IDH1 mutation and MGMT promoter methylation are associated with longer survival. We investigated the ability of imaging correlates to serve as noninvasive biomarkers for these molecularly defined GBM subtypes.

Cited by 269 publications

References 48 publications

Prognostic Value of MGMT Promoter Methylation and TP53 Mutation in Glioblastomas Depends on IDH1 Mutation

Prognostic Value of MGMT Promoter Methylation and TP53 Mutation in Glioblastomas Depends on IDH1 Mutation

MR Imaging–Based Analysis of Glioblastoma Multiforme: Estimation ofIDH1Mutation Status

Genetic alterations of IDH1 and Vegf in brain tumors

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