Mutations in IDH1 and TERT genes in gliomas and the prognosis value

DIANA PARMA; FUNES PEDRO; DANIELA MOGGIA; LEONELA LUCE; FERRER MARCELA; FLORENCIA GILIBERTO,; , SZIJAN IRENE

Congreso; SAIC-SAI-SAFIS 2018 REUNIÓN CONJUNTA DE LAS SOCIEDADES DE BIOCIENCIAS LXIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2018

MUTATIONS IN IDH1 AND TERT GENES IN GLIOMAS AND THE PROGNOSIS VALUEParma D., Funes P., Moggia D., Luce L., Ferrer M., Giliberto F., Szijan I.Gliomas are the largest group of aggressive primary CNS tumors, they occur predominantly in adults. Purpose: correlation of mutations in isocytratedehydrogenase (IDH1) and telomerase reverse transcriptase (TERT) genes with tumor progression. DNA was isolated from tumor and blood for PCR amplification of IDH1 exon 6 and TERT promoter. PCR products were sequenced to identify the most frequent mutation in codon 132 of IDH1 and the C to T transitions at -124 and -146bp upstream the TERT ATG codon. Clinical data included age, gender, symptoms, tumor localization, histopathology, tumor growth and survival. Nineteen cases with an average age of 49 years were studied, 7 patients presented with low grade glioma and 12 patients presented with high grade. These 12 patients did not show mutations in IDH1 and showed tumor growth, whereas six patients with low grade glioma had a mutated IDH1 and showed no tumor growth. Mutations in TERT gene were identified in 7 out of 17 analyzed patients, they were C to T transition at -146bp, 4 of these patients had grade 4 glioma, 2 showed tumor growth and one of them died 3 months after surgery. Six patients with grade 4 glioma did not carry mutations in TERT gene. Twelve tumors showed a polymorphism C to T transition at -245bp which was also present in blood. Neither IDH1 nor TERT mutations were found in constitutional DNA. Comparison between IDH1 and TERT mutations indicated a correlation between the wild type state of IDH1 and the presence of mutation in TERT in four of the studied cases and these data were related to the high tumor grade. Our results point out that the presence of mutations in IDH1 can be used as a good prognosis. Analysis of IDH1 and TERT mutations is valuable in prediction of patient´s evolution and chemotherapy response.