Related Experiment Video
Updated: Apr 4, 2026
Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
The distribution of BRAF gene fusions in solid tumors and response to targeted therapy
Jeffrey S Ross1,2, Kai Wang1, Juliann Chmielecki1
1Foundation Medicine, Inc., Cambridge, MA.
Abstract:
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 < 0.0001), Spitzoid (75%) vs. nonSpitzoid melanomas (1%; p = 0.0001), acinar (67%) vs. nonacinar pancreatic cancers (<1%; p < 0.0001) and papillary (3%) vs. nonpapillary thyroid cancers (0%; p < 0.03). Clinical responses to trametinib and sorafenib are presented. In conclusion, BRAF fusions are rare driver alterations in a wide variety of malignant neoplasms, but enriched in Spitzoid melanoma, pilocytic astrocytomas, pancreatic acinar and papillary thyroid cancers.
Insights
BRAF gene fusions are rare driver alterations in various cancers, identified through comprehensive genomic profiling. These fusions are notably enriched in specific subtypes of melanoma, glioma, pancreatic, and thyroid cancers.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The BRAF V600E mutation is a known therapeutic target in melanoma.
- BRAF gene fusions have not been extensively studied as potential anticancer drug targets.
- Comprehensive genomic profiling enables the identification of novel driver alterations in cancer.
Purpose of the Study:
- To investigate the prevalence and characteristics of BRAF gene fusions across a wide spectrum of tumors.
- To identify specific cancer types and subtypes where BRAF fusions are enriched.
- To explore the potential of BRAF fusions as actionable targets for novel therapies.
Main Methods:
- Utilized FoundationOne™ or FoundationOne Heme™ comprehensive genomic profiling assays.
- Analyzed a cohort of 20,573 tumors for the presence of BRAF gene fusions.
- Characterized the fusion partners and tumor types associated with identified BRAF fusions.
Main Results:
- BRAF fusions were identified in 55 (0.3%) of 20,573 tumors across 12 tumor types.
- Twenty novel BRAF fusions were discovered, with 69% involving unique 5' fusion partners.
- BRAF fusions were significantly enriched in pilocytic gliomas, Spitzoid melanomas, acinar pancreatic cancers, and papillary thyroid cancers.
Conclusions:
- BRAF fusions represent rare but significant driver alterations in diverse malignant neoplasms.
- The enrichment of BRAF fusions in specific tumor subtypes suggests potential targeted therapy opportunities.
- Further investigation into BRAF fusions may lead to the development of novel BRAF inhibitor-based treatment strategies.
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