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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
PubMed
Abstract

Insights

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.
Keywords:
BRAFCategorizationKinase-impairedMelanomaNRAS

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