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

BRAF V600E mutational load as a prognosis biomarker in malignant melanoma

Arrate Sevilla  1 , M Celia Morales  2 , Pilar A Ezkurra  2   3 , Javier Rasero  3 , Verónica Velasco  3   4 , Goikoane Cancho-Galan  3   5 , Ana Sánchez-Diez  3   6 , Karmele Mujika  7   8 , Cristina Penas  2 , Isabel Smith  9 , Aintzane Asumendi  2   3 , Jesús M Cortés  2   3   10 , Maria Dolores Boyano  2   3 , Santos Alonso  1
Affiliations

BRAF V600E mutational load as a prognosis biomarker in malignant melanoma

Arrate Sevilla et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Immunohistochemistry (IHC) and digital PCR (dPCR) results from 3 samples.
A-C) Immunohistochemical staining of sections of paraffin-embedded biopsies for BRAF V600E (VE1 antibody) contrasted with hematoxylin-eosin staining. D-H) dPCR results for BRAF V600E mutation. D-F) for c.1799T>A mutation and G-H) c.1799_1800TG>AA mutation. Every dot represents a well in the chip: In blue, wells containing BRAF V600E alleles; in red wells containing wild-type BRAF; in green, wells containing both V600E and wild-type forms, and in yellow, wells with no DNA molecules. Sample 1: IHC: V600E BRAF positive and dPCR: high mutational load for c.1799T>A. Sample 2: IHC: V600E BRAF negative. dPCR: negative for c.1799T>A and low mutational load for c.1799_1800TG>AA mutation. Sample 3: IHC: V600E BRAF positive. dPCR: Really low mutational load for c.1799T>A, but high for c.1799_1800TG>AA mutation.
See this image and copyright information in PMC

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