Detalle Publicación

Molecular study of long-term survivors of glioblastoma by gene-targeted next-generation sequencing

Autores: Cantero, D.; Rodríguez de Lope, A.; Moreno de la Presa, R.; Sepulveda, J. M; Borras, J. M.; Sáez Castresana, Javier; D'Haene, N. ; Garcia, J. F.; Salmon, I.; Mollejo, M.; Rey, J. A.; Hernandez-Lain, A.; Melendez, B. (Autor de correspondencia)
ISSN: 0022-3069
Volumen: 77
Número: 8
Páginas: 710 - 716
Fecha de publicación: 2018
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.