Genetic alterations of IDH1 and Vegf in brain tumors.

Silvia Veganzones,Anna González‐Neira,Jesús Vaquero,Virginia De La Orden,María Luisa González,Horacio Mario Zimman,Náyade Del Prado,Beatriz Mediero,Lucía Requejo,Alvaro Pérez‐Zamarrón,Armando Martínez,Carmen Rodríguez García,Gregorio Rodríguez‐Boto,Marisa L Maestro,Raquel Gutiérrez‐González

doi:10.1002/brb3.718

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.

Highlights

Primary brain tumors account for 85%–90% of all primary central nervous system tumors (Mehta, Vogelbaum, Chang, & Patel, 2011), with an estimate prevalence and mortality of 1.8% and 2.3% of all cancers respectively (Ferlay et al, 2015)
Few studies analyzing VEFG on brain tumors have been carried out, today it is believed that the +936 C/T polymorphism is associated with low-grade gliomas, being a risk factor for progression (Quon et al, 2010)
In the present study we assess the frequency of IDH1R132H mutation and vascular endothelial growth factor (VEGF) +936 C/T polymorphism in a Spanish population carrying brain tumors, their association with clinical variables, overall survival (OS) and progression free survival (PFS)

Summary

| INTRODUCTION

Primary brain tumors account for 85%–90% of all primary central nervous system tumors (Mehta, Vogelbaum, Chang, & Patel, 2011), with an estimate prevalence and mortality of 1.8% and 2.3% of all cancers respectively (Ferlay et al, 2015). Mutated enzyme IDH1 catalyzes the reduction in α-KG to NADP-dependent R2- hydroxyglutarate (R2-HG), which causes a reduction in GSH and in prolyl oxidases levels and promotes the accumulation of hypoxia inducible factor (HIF-1α; Ducray et al, 2011; Parsons et al, 2008; Thota et al, 2012). Few studies analyzing VEFG on brain tumors have been carried out, today it is believed that the +936 C/T polymorphism is associated with low-grade gliomas, being a risk factor for progression (Quon et al, 2010). In the present study we assess the frequency of IDH1R132H mutation and VEGF +936 C/T polymorphism in a Spanish population carrying brain tumors, their association with clinical variables, overall survival (OS) and progression free survival (PFS)

| MATERIAL AND METHODS

Findings

| DISCUSSION

| CONCLUSIONS