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
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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