Histone H3.3 K27M and G34R/W/V changes in different pediatric cerebral neoplasms

Abstract

Tumors of the central nervous system (CNS) are a frequent cause of death in children and adolescents. Recently, changes in epigenetic mechanisms have been implicated in the oncogenesis of high-grade gliomas (HGG) in children. Mutations in histone H3F3A (K27M or G34R/V/W) were related to tumor location and prognosis of pediatric gliomas. Clinically, several preclinical and clinical studies attempt to evaluate the effect of histone-modifying drugs in the treatment of these highly malignant neoplasms. The objective of the present study is to standardize methods to analyses these mutations by PCR; RT-PCR and gene sequencing (SANGER) in a cohort of pediatric brain tumors from patients treated at the clinical hospital of the Faculty of Medicine - Ribeirão Preto - USP in the last 15 years. It is also intended to validate the presence and frequency of these mutations in a cohort of Brazilian patients with HGG, as well as to investigate the presence of these mutations in different tumors other than pediatric HGG.