Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, UPV/EHU, Leioa, Spain.
Department of Cell Biology and Histology, Faculty of Medicine and Nursing, UPV/EHU, Leioa, Spain.
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.
分析黑色素瘤中驱动突变的突变负荷可以提供有关其进展的有价值的信息。我们旨在分析不同阶段黑色素瘤患者活检中 BRAF V600E 突变负荷的异质性,并研究其作为预后因素的潜力。通过数字 PCR 分析了 78 例不同阶段黑色素瘤患者和 10 例痣的 BRAF V600E 突变负荷。比较了不同阶段活检中的 BRAF V600E 负荷。结果显示 V600E 的负荷存在很大的变异性(0%-81%)。有趣的是,我们观察到早期和晚期黑色素瘤阶段之间 V600E 负荷存在显著差异,即 BRAF V600E 突变负荷与黑色素瘤进展呈负相关。此外,机器学习方法表明,BRAF V600E 的突变负荷可以很好地预测 II 期患者的转移。我们的结果表明,BRAF V600E 是 II 期患者预后的有前途的生物标志物。