Recurrent somatic BRAF insertion (p.V504_R506dup): a tumor marker and a potential therapeutic target in pilocytic astrocytoma
| Autor: | Chantal Richer, Monia Marzouki, Sébastien Perreault, Daniel Sinnett, Fida Khater, Anne-Marie Roy, Pascal St-Onge, Jasmine Healy, Pauline Cassart, Sylvie Langlois, Mathieu Lajoie, Sonia Cellot, Nada Jabado, Nelson Piché |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Proto-Oncogene Proteins B-raf 0301 basic medicine Cancer Research Adolescent Cancer therapy Somatic cell Astrocytoma Biology medicine.disease_cause Article Cell Line 03 medical and health sciences 0302 clinical medicine Genes Duplicate Biomarkers Tumor Cancer genomics Genetics medicine Humans Cancer genetics Molecular Biology Tumor marker Mutation Pilocytic astrocytoma HEK 293 cells medicine.disease Molecular diagnostics CNS cancer HEK293 Cells 030104 developmental biology Protein kinase domain 030220 oncology & carcinogenesis Cancer research Tandem exon duplication Neoplasm Recurrence Local Biomarkers |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | Pilocytic astrocytoma (PA) is emerging as a tumor entity with dysregulated RAS/RAF/MEK/ERK signaling. In this study, we report the identification of a novel recurrent BRAF insertion (p.V504_R506dup) in five PA cases harboring exclusively this somatic tandem duplication. This recurrent alteration leads to an addition of three amino acids in the kinase domain of BRAF and has functional impact on activating MAPK phosphorylation. Importantly, we show that this mutation confers resistance to RAF inhibitors without changing effectiveness while downstream MEK inhibitors remain effective. Our results further emphasize the importance of BRAF alterations in PA and the need to characterize them in a given tumor as this can affect therapeutic strategies and their potential use as tumor marker in molecular diagnostics. |
| Databáze: | OpenAIRE |
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