Molecular Study of Long-Term Survivors of Glioblastoma by Gene-Targeted Next-Generation Sequencing

Journal of Neuropathology and Experimental Neurology
Diana CanteroBárbara Meléndez

Abstract

Glioblastoma (GBM) is the most common malignant adult primary brain tumor. Despite its high lethality, a small proportion of patients have a relatively long overall survival (OS). Here we report a study of a series of 74 GBM samples from 29 long-term survivors ([LTS] OS ≥36 months) and 45 non-LTS. Using next-generation sequencing, we analyzed genetic alterations in the genes most frequently altered in gliomas. Approximately 20% of LTS had a mutation in the IDH1 or IDH2 (IDH) genes, denoting the relevance of this molecular prognostic factor. A new molecular group of GBMs harbored alterations in ATRX or DAXX genes in the absence of driver IDH or H3F3A mutations. These patients tended to have a slightly better prognosis, to be younger at diagnosis, and to present frontal or temporal tumors, and, morphologically, to present giant tumor cells. A significant fraction of LTS GBM patients had tumors with 1 or more alterations in the relevant GBM signaling pathways (RTK/PI3K, TP53 and RB1). In these patients, the PDGFRA alteration is suggested to be a favorable molecular factor. Our findings here are relevant for developing future targeted therapies and for identifying molecular prognostic factors in GBM patients.

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Citations

Sep 19, 2019·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Shubhanchi NigamW Barry Edwards
Jan 18, 2020·Cancers·Berta Segura-CollarPilar Sánchez-Gómez
Aug 11, 2020·Acta Neuropathologica Communications·Laetitia LebrunIsabelle Salmon
Sep 22, 2020·Journal of Neuropathology and Experimental Neurology·Timothy E RichardsonJamie M Walker
May 12, 2019·Nature Reviews. Cancer·Flurina A M SanerDavid D L Bowtell
Jan 12, 2021·Neuro-oncology Advances·Sherise D FergusonAmy B Heimberger
Jun 1, 2021·Neuro-oncology Practice·Evan K NochAlexandra M Miller
Nov 7, 2020·Journal of Neurological Surgery. Part A, Central European Neurosurgery·Lei YuSongtao Qi

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