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Updated: Dec 9, 2025
07:49
Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
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Targetable BRAF and RAF1 Alterations in Advanced Pediatric Cancers
Andrew Rankin1, Adrienne Johnson1, Alison Roos1
1Foundation Medicine Inc., Cambridge, Massachusetts, USA.
The Oncologist
|September 12, 2020
Summary
Genomic profiling of 3,633 pediatric cancers revealed BRAF/RAF1 alterations in 6.1% of cases, primarily brain tumors. These findings support precision medicine approaches for pediatric oncology, including targeted BRAF therapies.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- RAF family kinases regulate cell growth and survival via the MAPK pathway.
- Identifying BRAF alterations is crucial for targeted therapy in pediatric cancers.
- Precision medicine integration in pediatric oncology remains limited.
Purpose of the Study:
- To characterize the landscape of BRAF and RAF1 genomic alterations in a large cohort of pediatric cancers.
- To identify potential therapeutic targets and inform precision medicine strategies for pediatric patients.
- To evaluate the clinical response to BRAF inhibitors in pediatric brain tumors.
Main Methods:
- Comprehensive genomic profiling of 3,633 pediatric cancer samples.
- Identification and classification of BRAF and RAF1 alterations (variants, fusions, indels).
- Analysis of tumor types associated with RAF alterations and clinical response to targeted therapies.
Main Results:
- BRAF or RAF1 alterations were found in 6.1% (221/3,633) of pediatric cancers, predominantly brain tumors (74.4%).
- Activating short variants (55.7%) and fusions (40.9%) were the most common alteration types.
- Seven RAF1 fusions, including two novel ones (TMF1-RAF1, SOX6-RAF1), were identified.
- A subset of pediatric brain tumor patients showed positive clinical response to BRAF inhibitors.
Conclusions:
- BRAF and RAF1 alterations are present across various pediatric cancers, particularly brain tumors.
- The identification of these alterations supports the use of targeted BRAF/MEK inhibitors in pediatric oncology.
- This study underscores the potential of precision medicine to improve treatment outcomes for children with cancer.
Keywords:
BiomarkersBrain neoplasmsLeukemiaPediatricsPrecision medicineProteins B-rafProto-oncogeneTumorMore Related Videos
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