Biological insights into BRAFV600 mutations in melanoma patient: Not mere therapeutic targets
Giuseppina Improta, Giuseppe Pelosi, Elena Tamborini, Marco Donia, Mario Santinami, Filippo de Braud, Filippo Fraggetta, Giuseppina Improta, Giuseppe Pelosi, Elena Tamborini, Marco Donia, Mario Santinami, Filippo de Braud, Filippo Fraggetta
Abstract
Some experimental evidence indicates that uncommon BRAF mutations consisting in the substitution of 2 adjacent nucleotides within codon 600 are in a cis configuration and associate with BRAF gene amplification. These findings suggest that BRAFV600 mutations are unlikely to occur as homozygous alterations in clinical melanoma samples, with gene amplification perhaps contributing to mask the heterozygous state.
Keywords: BRAF; MHC; homozygosis; immunotherapy; melanoma; vemurafenib.
Figures
Figure 1. Vemurafenib increases interferon γ-induced MHC expression on melanoma cells harboring a masked heterozygous BRAFV600 mutation. (A) MHC expression levels are higher in wild-type melanoma cells that in cells bearing a BRAFV600 mutation. (B) Mutant BRAFV600 suppresses the expression of MHC molecules on the cell surface. (C) The administration of BRAF inhibitors (BRAFis) promotes the interferon γ (IFNγ)-induced expression of MHC molecules by melanoma cells that harbor a “masked” heterozygous BRAFV600 mutation in the context of BRAF amplification or loss-of-heterozygosity (LOH). ERK, extracellular signal-regulated kinase; MEK, MAPK/ERK kinase; TCR, T-cell receptor.
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Source: PubMed