BRAF V600E mutational load as a prognosis biomarker in malignant melanoma

PLoS One. 2020 Mar 13;15(3):e0230136. doi: 10.1371/journal.pone.0230136. eCollection 2020.


Analyzing the mutational load of driver mutations in melanoma could provide valuable information regarding its progression. We aimed at analyzing the heterogeneity of mutational load of BRAF V600E in biopsies of melanoma patients of different stages, and investigating its potential as a prognosis factor. Mutational load of BRAF V600E was analyzed by digital PCR in 78 biopsies of melanoma patients of different stages and 10 nevi. The BRAF V600E load was compared among biopsies of different stages. Results showed a great variability in the load of V600E (0%-81%). Interestingly, we observed a significant difference in the load of V600E between the early and late melanoma stages, in the sense of an inverse correlation between BRAF V600E mutational load and melanoma progression. In addition, a machine learning approach showed that the mutational load of BRAF V600E could be a good predictor of metastasis in stage II patients. Our results suggest that BRAF V600E is a promising biomarker of prognosis in stage II patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • DNA Mutational Analysis / methods
  • Female
  • Humans
  • Machine Learning
  • Male
  • Melanoma* / genetics
  • Melanoma* / pathology
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Nevus, Pigmented
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology


  • Biomarkers, Tumor
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf

Supplementary concepts

  • Melanoma, Cutaneous Malignant

Grant support

This research was supported by the Basque Government (grants ELKARTEK- KK2016-036 and KK2017-041 to MDB, grant IT1138-16 to SA and predoctoral fellowship PRE_2014_1_419 to AS), and by the University of the Basque Country (UPV/EHU) (grant GIU17/066). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.