The distribution of BRAF gene fusions in solid tumors and response to targeted therapy
Autor: | Jeffrey S. Ross, Kai Wang, Juliann Chmielecki, Laurie Gay, Adrienne Johnson, Jacob Chudnovsky, Roman Yelensky, Doron Lipson, Siraj M Ali, Julia A. Elvin, Jo‐Anne Vergilio, Steven Roels, Vincent A Miller, Brooke N. Nakamura, Adam Gray, Michael K Wong, Philip J Stephens |
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Rok vydání: | 2015 |
Předmět: |
Male
0301 basic medicine Oncology Cancer Research Oncogene Proteins Fusion medicine.medical_treatment Targeted therapy Sptizoid melanoma 0302 clinical medicine Neoplasms Molecular Targeted Therapy pilocytic astrocytoma Child Research Articles Aged 80 and over Trametinib Pilocytic astrocytoma comprehensive genomic profiling Melanoma Thyroid Middle Aged Sorafenib solid tumors targeted therapy Treatment Outcome medicine.anatomical_structure Child Preschool NGS 030220 oncology & carcinogenesis Female medicine.drug Adult Niacinamide Proto-Oncogene Proteins B-raf medicine.medical_specialty Adolescent Pyridones BRAF fusions Antineoplastic Agents Pyrimidinones Cancer Genetics and Epigenetics Young Adult 03 medical and health sciences pancreatic acinar carcinoma Internal medicine medicine Humans cancer Protein Kinase Inhibitors neoplasms Aged business.industry Gene Expression Profiling Phenylurea Compounds Infant Cancer medicine.disease Gene expression profiling 030104 developmental biology Transcriptome business |
Zdroj: | International Journal of Cancer |
ISSN: | 1097-0215 0020-7136 |
Popis: | Although the BRAF V600E base substitution is an approved target for the BRAF inhibitors in melanoma, BRAF gene fusions have not been investigated as anticancer drug targets. In our study, a wide variety of tumors underwent comprehensive genomic profiling for hundreds of known cancer genes using the FoundationOne™ or FoundationOne Heme™ comprehensive genomic profiling assays. BRAF fusions involving the intact in‐frame BRAF kinase domain were observed in 55 (0.3%) of 20,573 tumors, across 12 distinct tumor types, including 20 novel BRAF fusions. These comprised 29 unique 5′ fusion partners, of which 31% (9) were known and 69% (20) were novel. BRAF fusions included 3% (14/531) of melanomas; 2% (15/701) of gliomas; 1.0% (3/294) of thyroid cancers; 0.3% (3/1,062) pancreatic carcinomas; 0.2% (8/4,013) nonsmall‐cell lung cancers and 0.2% (4/2,154) of colorectal cancers, and were enriched in pilocytic (30%) vs. nonpilocytic gliomas (1%; p What's new? New results may help target a rare genetic alteration that promotes cancer. Activation of the BRAF gene is already known to spur tumor growth, and usually that activation results from a single amino acid substitution. BRAF‐inhibiting treatments, then, target that mutation. However, in some cases, BRAF gets revved up by a gene fusion. In our study, the authors tested 20,000 tumors and identified 55 BRAF gene fusions in 12 different tumor types. They found the gene fusions occurred more frequently in certain histologic subtypes, information which will help guide treatment strategies for patients with these tumor subtypes. |
Databáze: | OpenAIRE |
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