Estudio de mutaciones en los genes IDH1 e IDH2 en una muestra de gliomas de población colombiana / Study of mutations in IDH1 and IDH2 genes in a sample of gliomas from Colombian population

Resumen Introducción. Los gliomas son los tumores primarios más comunes del sistema nervioso central y se clasifican de I a IV según su grado de malignidad. En recientes investigaciones se ha encontrado que su aparición está relacionada con mutaciones en el exón 4 de los genes que codifican las deshidrogenasas de isocitrato 1 y 2 (IDH1: codón 132; IDH2: codón 172). Objetivo. Determinar la frecuencia de mutaciones en los genes IDH1 e IDH2 en una muestra de gliomas de pacientes colombianos. Materiales y métodos. La extracción de ADN se hizo a partir de tejido tumoral. El exón 4 de los genes IDH1 e IDH2 se amplificó mediante PCR utilizando iniciadores específicos y, posteriormente, se secuenciaron. Para la determinación de las mutaciones, se emplearon los programas 4Peaksy MAFFT. Resultados. Se determinó la presencia de mutaciones en el gen IDH1 en el 34 % de las muestras, con predominio de la mutación no sinónima R132H. En el 7,5 % de los casos se detectaron mutaciones en el gen IDH2, principalmente las mutaciones no sinónimas R172K y R172W. Conclusiones. La frecuencia de mutaciones en los genes IDH1 e IDH2 en la muestra fue similar a la reportada en otros estudios. El análisis de estas mutaciones puede ser importante como factor pronóstico y para su uso como potenciales blancos terapéuticos en gliomas.

Abstract Introduction: Gliomas are the most common primary tumors of the central nervous system and, according to their malignancy, they are graded from I to IV. Recent studies have found that there is an association between gliomas and mutations in exon 4 of genes that codify for isocitrate dehydrogenases 1 and 2 (IDH1: codon 132; IDH2: codon 172). Objective: To establish the frequency of mutations in IDH1 and IDH2 in a sample of gliomas from Colombian population. Materials and methods: DNA was extracted from tumor tissue. The exon 4 of IDH1 and IDH2 was amplified by PCR using specific primers and subsequently sequenced. Mutations were determined using the 4Peaks MAFFT programs. Results: We found mutations in the IDH1 gene in 34% of the glioma samples, with a predominance of the nonsynonymous mutation R132H. Mutations in the IDH2 gene were found in 7.5% of cases, with a predominance of the nonsynonymous R172K and R172W mutations. Conclusions: The frequency of mutations in the IDH1 and IDH2 genes in the sample was similar to that reported in other studies. The analysis of these mutations may be important to establish prognostic factors and for the development of future therapeutic targets in gliomas.

EGFR, p53, IDH-1 and MDM2 immunohistochemical analysis in glioblastoma: therapeutic and prognostic correlation / Análise imunoistoquímica para EGFR, p53, IDH-1 e MDM2 em glioblastoma: correlação terapêutica e prognóstica

We studied 36 glioblastoma cases at HC-UNICAMP from 2008 to 2012 and classified the immunohistochemical distribution of the wild-type epidermal growth factor receptor (EGFR), mutated forms of p53 protein and isocitrate dehydrogenase-1 (IDH-1) and murine double protein 2 (MDM2). Immunostaining findings were correlated with clinical data and response to treatment (surgery, chemotherapy and radiotherapy). About 97% of the tumors were primary, most of them localized in the frontal lobe. Mean time free of clinical or symptomatic disease and free time of radiological disease were 7.56 and 7.14 months, respectively. We observed a significant positive correlation between expressions of p53 and MDM2, EGFR and MDM2. Clinical, radiological and overall survivals also showed a significant positive correlation. p53 staining and clinical survival showed a significant negative correlation. The current series provides clinical and histopathological data that contribute to knowledge on glioblastoma in Brazilians.

Estudamos 36 casos de glioblastoma acompanhados no HC-UNICAMP de 2008 a 2012 e classificamos a marcação imunoistoquímica da forma selvagem do receptor do fator de crescimento epidérmico (EGFR), formas mutantes da proteína p53 e isocitrato desidrogenase-1 (IDH-1) e proteína murina dupla 2 (MDM2). Os resultados de imunoistoquímica foram correlacionados com dados clínicos e resposta ao tratamento (cirurgia, quimioterapia e radioterapia). Cerca de 97% dos tumores foram primários, grande parte localizada no lobo frontal. O tempo médio livre de doença clínica ou sintomática e o tempo livre de doença radiológica foram de 7.56 e 7.14 meses, respectivamente. Observou-se correlação positiva entre a expressão das proteínas p53 e MDM2, EGFR e MDM2. Sobrevivências clínica, radiológica e global também mostraram correlação positiva e significativa. A expressão para p53 e sobrevivência clínica mostrou correlação negativa. O estudo fornece dados clínicos e histopatológicos que contribuem para o conhecimento sobre glioblastoma em brasileiros.