Recurrent somatic BRAF insertion (p.V504_R506dup): a tumor marker and a potential therapeutic target in pilocytic astrocytoma
| العنوان: | Recurrent somatic BRAF insertion (p.V504_R506dup): a tumor marker and a potential therapeutic target in pilocytic astrocytoma |
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| المؤلفون: | 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 |
| المصدر: | Oncogene |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::44e8a310e50f4deaca2eff8726175188Test https://doi.org/10.1038/s41388-018-0623-3Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....44e8a310e50f4deaca2eff8726175188 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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