Detailed imaging and genetic analysis reveal a secondary BRAFL505H resistance mutation and extensive intrapatient heterogeneity in metastatic BRAF mutant melanoma patients treated with vemurafenib. (7th January 2015)

• Record Type: Journal Article
• Authors: Hoogstraat, Marlous; Gadellaa‐van Hooijdonk, Christa G.; Ubink, Inge; Besselink, Nicolle J. M.; Pieterse, Mark; Veldhuis, Wouter; van Stralen, Marijn; Meijer, Eelco F. J.; Willems, Stefan M.; Hadders, Michael A.; Kuilman, Thomas; Krijgsman, Oscar; Peeper, Daniel S.; Koudijs, Marco J.; Cuppen, Edwin; Voest, Emile E.; Lolkema, Martijn P.
• Is Part Of: Pigment cell & melanoma research. Volume 28:Number 3(2015:May)
• Page Start: 318
• Page End: 323
• Publication Date: 2015-01-07
• Subjects: Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12347
• Languages: English
• ISSNs: 1755-1471

Abstract

<abstract abstract-type="main" id="pcmr12347-abs-0001"> <title>Summary</title> <p>Resistance to treatment is the main problem of targeted treatment for cancer. We followed ten patients during treatment with vemurafenib, by three‐dimensional imaging. In all patients, only a subset of lesions progressed. Next‐generation DNA sequencing was performed on sequential biopsies in four patients to uncover mechanisms of resistance. In two patients, we identified mutations that explained resistance to vemurafenib; one of these patients had a secondary <italic>BRAF</italic> L505H mutation. This is the first observation of a secondary <italic>BRAF</italic> mutation in a vemurafenib‐resistant patient‐derived melanoma sample, which confirms the potential importance of the <italic>BRAF</italic> L505H mutation in the development of therapy resistance. Moreover, this study hints toward an important role for tumor heterogeneity in determining the outcome of targeted treatments.</p> </abstract>