BRAF V600E mutational load as a prognosis biomarker in malignant melanoma

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.

BRAFV600E Mutant Allele Frequency (MAF) Influences Melanoma Clinicopathologic Characteristics

“…In recent years, controversial results have been obtained by studies which related the BRAF V600E MAF of melanoma tumors with clinicopathological and prognostic characteristics as well as the melanoma response, in order to target therapies [15,[23][24][25][26]. All these studies analyzed the MAF value of one specific region for each tumor, so we wanted to know whether the variation degree of BRAF V600E MAF within different regions of the same tumor could influence these characteristics.…”

“…Besides the usefulness of the BRAF V600E driver mutation as a therapeutic target, a recent study has suggested that the mutational load of BRAF V600E is a possible prognostic biomarker [15], expanding the classical histopathological prognostic criteria such as ulceration, Breslow, Clark or mitotic indexes [1,[16][17][18][19][20][21][22]. Moreover, some studies in recent years have attempted to relate the mutational load to the response in order to target therapies, but controversial results have been obtained [23][24][25][26].…”

Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions

“…In patients with BRAF mutation, the ideal sequence of treatment or the choice of sequence of combination is still an open issue [4,31,98]. The results of two large ongoing studies are awaited.…”

“…In 2005, Uhara et al reported an elevate detection of the BRAF mutation in patients with melanoma without chronic sun-induced damage [ 28 , 29 ]. Further research showed that nearly 40-50% of cutaneous melanomas have mutations in BRAF, a gene that belongs to the family of mitogen activated protein kinase (MAPK) and codes for a serine/threonine protein kinase constituting part of RAS-RAF-MEK [ 30 , 31 ]. BRAF activation induces the phosphorylation of extracellular signal-regulated kinases (ERK) that constitute the most common mutated isoforms in cancer [ 32 ].…”

Survivin as a biological biomarker for diagnosis and therapy

“…Other biomolecules besides SVN are already used extensively as biomarkers for cancer prediction or prognosis. Well-known examples include EGFR in molecular apocrine breast cancer (MABC) [69], VEGF in colorectal cancer [70] and oncogenic BRAF mutation [71] and KRAS mutations in pancreatic cancer [72]. Since SVN is also upregulated in autoimmunity and inflammation, for tumor diagnosis, it is necessary to combine an SVN test with other biomarkers.…”