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

Journal of neuropathology and experimental neurology (2018-07-17)
Diana Cantero, Ángel Rodríguez de Lope, Raquel Moreno de la Presa, Juan M Sepúlveda, José M Borrás, Javier S Castresana, Nicky D'Haene, Juan F García, Isabelle Salmon, Manuela Mollejo, Juan A Rey, Aurelio Hernández-Laín, Bárbara 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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Anti-ATRX antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution