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Response to BRAF/MEK Inhibition in A598_T599insV BRAF Mutated Melanoma

Journal article
Authors Sara Bjursten
Christoffer Vannas
Stefan Filges
Florian Puls
Ankur Pandita
Henrik Fagman
Anders Ståhlberg
Max Levin
Published in Case Reports in Oncology
Volume 12
Issue 3
Pages 872-879
Publication year 2019
Published at Institute of Clinical Sciences, Department of Oncology
Sahlgrenska Cancer Center
Department of Laboratory Medicine
Wallenberg Centre for Molecular and Translational Medicine
Pages 872-879
Language en
Links https://doi.org/10.1159/000504291
Keywords BRAF A598_T599insV, Circulating cell-free tumor DNA, Melanoma, Targeted therapy
Subject categories Cancer and Oncology

Abstract

Approximately 50% of patients with metastatic melanoma harbor an activating BRAF mutation. Tumors with activating mutation BRAF gene proliferate excessively and can be treated with targeted BRAF-inhibitors in combination with MEK inhibitors. The most common BRAF mutation occurs at amino acid position 600. Other BRAF mutations are rare and their predictive value for treatment response to BRAF/MEK inhibition is low. Here, we report on a patient with a BRAF A598_T599insV mutated melanoma, a mutation that has only been described in one previous melanoma patient in which the treatment response to BRAF/MEK inhibition was transient. Our patient had a large ulcerated metastasis that showed a durable complete response implying that BRAF/MEK inhibition should be considered a treatment option for this mutation. We analyzed circulating cell-free tumor DNA (ctDNA) carrying the BRAF A598_T599insV mutation throughout treatment. The allele frequency of BRAF A598_T599insV decreased during regression of the tumors, indicating that this method has potential to monitor treatment response. Our case demonstrates durable response to BRAF/MEK inhibition in a melanoma patient carrying a BRAF A598_T599insV mutation. In addition, we show that allele frequency analysis of A598_T599insV mutation in blood using ultrasensitive sequencing can be used to monitor treatment response.

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