Diagnostic moléculaire des gliomes diffus

Abstract

Diffuse gliomas are the most common primitive tumors of the central nervous system (CNS). Those are infîltrative neoplasms with a dismal prognosis and a tendency to malignant transformation. The 2016 WHO classification of CNS tumors distin-guishes diffuse astrocytomas from oligodendrogliomas. Diffuse gliomas are classified according to the status of IDH1/2 genes since IDH1/2 mutations are associated with a better prognosis. Among the IDH-mutant gliomas, oligodendrogliomas display a combined loss of chromosomal arms 1p and 19q (1p/19q codeletion) whereas diffuse astrocytomas harbor mutation of ATRX and TP53 genes. The 1 p/19q codeletion is associated with a longer survival (> 15 years). Among the IDH-wild type diffuse gliomas, glioblastomas (GB) represent the most frequent and most aggressive form, with a median survival of 15 months. GB display EGFR gene amplification, chromosome 7 gain and chromosome 10 loss. Diffuse midline gliomas (brainstem), most common in children, habor a K27M mutation of histone genes H3F3/HIST1H3B, associated with a very short survival (< 1 year). The G34R/V mutation of H3F3 gene is present in diffuse gliomas of the cerebral hemispheres in adolescents. Such a histomolecular classification of diffuse gliomas is more objective than histology alone and will be the basis of personalized medicine in the years to come.