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Detection of Rare Mutations in CtDNA Using Next Generation Sequencing
Published on: August 24, 2017
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Clinical mutational profiling and categorization of BRAF mutations in melanomas using next generation sequencing
Parvez M Lokhandwala1, Li-Hui Tseng2,3, Erika Rodriguez2
1Department of Pathology, Johns Hopkins University School of Medicine, Johns Hopkins University School of Medicine, 1812 Ashland Ave, Suite 200, Baltimore, MD, 21205, USA. plokhan1@jhmi.edu.
BMC Cancer
|July 7, 2019
Summary
This study analyzed BRAF mutations in melanomas using next-generation sequencing (NGS), classifying them into three classes. Class-3 BRAF mutations were associated with coexisting RAS mutations and specific tumor locations, suggesting chronic sun damage.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Analysis of actionable mutations in melanoma is standard care.
- A new classification scheme categorizes BRAF mutations by MAPK pathway activation mechanisms.
Purpose of the Study:
- To categorize BRAF mutations (class-1, -2, -3) in a large melanoma cohort.
- To analyze coexisting mutations and clinical characteristics of BRAF mutation classes.
Main Methods:
- Next-generation sequencing (NGS) analyzed BRAF, KIT, NRAS, and PIK3CA mutations in 446 melanomas.
- KRAS and HRAS were analyzed for coexisting BRAF and RAS mutations.
- BRAF mutations were classified into class-1, -2, and -3 based on a proposed scheme.
Main Results:
- NGS showed high sensitivity, detecting mutations in BRAF (42%), NRAS (25%), KIT (4.9%), and PIK3CA (2.7%).
- Class-1, -2, and -3 BRAF mutations represented 77%, 7.4%, and 12% of all BRAF mutations, respectively.
- Class-3 mutations frequently coexisted with RAS mutations and were associated with older age and specific tumor locations, suggesting a role for chronic sun damage.
Conclusions:
- This study provides a comprehensive categorization of BRAF mutation classes in melanoma.
- Further research is needed to understand clinical outcomes and targeted therapy benefits for each BRAF mutation class.
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