Mutations V600 de BRAF dans le mélanome : comparaison de l’immuno-histochimie et de la biologie moléculaire

Bay, Ali; Hasna, Jessy; Attencourt, Christophe; Althakfi, Wajd Ahmed; Sockeel, Marie; Sevestre, Henri; Gubler, Brigitte; Trudel, Stéphanie

doi:10.1016/j.annpat.2014.08.007

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“…This is explained by the fact that the forward extension primer for V600E specifically targets the second nucleotide (T) in codon 600 (G T G), which in our case was also substituted for an A (G AT ), as in the V600E mutation (G A G). However, in a retrospective study of 47 metastatic melanoma from our centre, we have compared the V600 mutation detection by molecular techniques with the BRAF V600E mutant protein expression by immunohistochemical analysis using highly specific anti- BRAF V600E monoclonal antibodies and no other cases of misidentified p.V600E mutation was found [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

The clinical response to vemurafenib in a patient with a rare BRAF V600DK601del mutation-positive melanoma

et al. 2014

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BackgroundMutations in the activation segment of the v-raf murine sarcoma viral oncogene homolog B (BRAF) gene are present in approximately 50% of melanomas. The selective BRAF inhibitor vemurafenib has demonstrated significant clinical benefits in patients with melanomas harboring the most common mutations (V600E, V600K and V600R). However, the clinical activity of BRAF inhibitors in patients with rare mutations of codon 600 and the surrounding codons has not been documented.Case presentationWe used the BRAF inhibitor vemurafenib to treat a patient presenting a rare p.V600_K601delinsD-mutated melanoma. An objective response was evidenced by two months of progression-free survival. By cloning and sequencing BRAF exon 15, we confirmed that a dual mutation was present on a single allele and thus resulted in a BRAFV600DK601del mutant protein. We also performed an in silico crystal structure analysis of the mutated protein, in order to characterize the nature of the putative interaction between vemurafenib and the mutant protein.ConclusionThis clinical experience suggests that (i) patients with BRAFV600DK601del-mutation-positive melanoma can be treated successfully with the oral BRAF inhibitor vemurafenib and (ii) molecular screening in this context should encompass rare and complex mutations.

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Section: Discussionmentioning

confidence: 99%