Genetic alterations of IDH1 and Vegf in brain tumors

Abstract

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.

Isocitrate Dehydrogenase Mutations in Glioma: From Basic Discovery to Therapeutics Development

“…It was found that the mutations of IDH1/2 could promote the formation of the tumor microenvironment by increasing the expression of VEGF and make it suitable for glioblastoma stem cell development (24). Simultaneously, the expression of VEGF in the glioma group of the same level was higher than that of the non-mutation group (25, 26). It is worth noting that HIF-1α can initiate transcription of VEGF, and hypoxia can induce an increase in VEGF (26).…”

Assessment of Intratumoral Heterogeneity in Isolated Human Primary High-Grade Glioma: Cluster of Differentiation 133 and Cluster of Differentiation 15 Double Staining of Glioblastoma Subpopulations

“…Ki-67 was expressed in >10% cells and confirmed the proliferation activity of isolated tumor cells since Ki-67 is an important marker for cell proliferation in clinical practice [12]. Expression of IDH-1 R132H mutant suggests that the tumors are likely secondary tumors [15]. The expression of PD-L1 is tightly related to the pathological grade of glioma.…”

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“…No correlation with patient outcome was observed in CHL patients [4]. The T allele of VEGF +936C/T polymorphism is more common in primary tumors of the glioma, but there is no statistical relation with survival [5]. Angiogenesis commonly attributed to the anticrime and paracrine production of VEGF-A, which up regulates the VEGF signal transduction pathway, is a prominent feature of glioblastoma [11].…”

“…In recent years, there have been some renewed efforts to develop the novel treatments based on molecular targets of glioma. The identification of these factors that can predict survival is an important goal for treatment of these patients, and a large number of studies have shown that the expression of VEGF was obviously related to the pathological grade of the tumor [3][4][5][6][7]. However, in a review of the literatures, no studies reported the association between VEGF expression level and different ethnic populations with an identical pathological classification.…”