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Case Reports
. 2010 Jul 14:8:67.
doi: 10.1186/1479-5876-8-67.

Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032

Jill C Rubinstein  1 , Mario Sznol, Anna C Pavlick, Stephan Ariyan, Elaine Cheng, Antonella Bacchiocchi, Harriet M Kluger, Deepak Narayan, Ruth Halaban
Affiliations
Case Reports

Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032

Jill C Rubinstein et al. J Transl Med. .

Abstract

Activating mutations in BRAF kinase are common in melanomas. Clinical trials with PLX4032, the mutant-BRAF inhibitor, show promising preliminary results in patients selected for the presence of V600E mutation. However, activating V600K mutation is the other most common mutation, yet patients with this variant are currently excluded from the PLX4032 trials. Here we present evidence that a patient bearing the BRAF V600K mutation responded remarkably to PLX4032, suggesting that clinical trials should include all patients with activating BRAF V600E/K mutations.

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Figures

Figure 1
Figure 1
Chest wall lesions before treatment with PLX4032 (A) and on the first day of the fifth treatment cycle (B).
Figure 2
Figure 2
Electropherogram from Sanger dideoxy sequencing showing the patient's melanoma tumor BRAF codon 600 mutation (AAG/GTG), encoding V600K/WT protein.
See this image and copyright information in PMC

References

    1. Flaherty K, Puzanov I, Sosman J, Kim K, Ribas A, McArthur G, Lee RJ, Grippo JF, Nolop K, Chapman P. Phase I study of PLX4032: Proof of concept for V600E BRAF mutation as a therapeutic target in human cancer. J Clin Oncol (Meeting Abstracts) 2009;27:9000.
    1. Uribe P, Wistuba I, González S. BRAF mutation: a frequent event in benign, atypical, and malignant melanocytic lesions of the skin. Am J Dermatopathol. 2003;25:365–370. doi: 10.1097/00000372-200310000-00001. - DOI - PubMed
    1. Poynter J, Elder J, Fullen D, Nair R, Soengas M, Johnson T, Redman B, Thomas N, Gruber S. BRAF and NRAS mutations in melanoma and melanocytic nevi. Melanoma Res. 2006;16:267–273. doi: 10.1097/01.cmr.0000222600.73179.f3. - DOI - PubMed
    1. Sala E, Mologni L, Truffa S, Gaetano C, Bollag G, Gambacorti-Passerini C. BRAF silencing by short hairpin RNA or chemical blockade by PLX4032 leads to different responses in melanoma and thyroid carcinoma cells. Mol Cancer Res. 2008;6:751–759. doi: 10.1158/1541-7786.MCR-07-2001. - DOI - PubMed
    1. Halaban R, Zhang W, Bacchiocchi A, Cheng E, Parisi F, Ariyan S, Krauthammer M, McCusker J, Kluger Y, Sznol M. PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells. Pigment Cell Melanoma Res. 2010;23:190–200. - PMC - PubMed