Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered BRAF transcript splicing

Biomarker Research
Gulietta M PupoHelen Rizos

Abstract

Alternate BRAF splicing is the most common mechanism of acquired resistance to BRAF inhibitor treatment in melanoma. Recently, alternate BRAF exon 4-8 splicing was shown to involve an intronic mutation, located 51 nucleotides upstream of BRAF exon 9 within a predicted splicing branch point. This intronic mutation was identified in a single cell line but has not been examined in vivo. Herein we demonstrate that in three melanomas biopsied from patients with acquired resistance to BRAF inhibitors, alternate BRAF exon 4-8 splicing is not associated with this intronic branch point mutation. We also confirm that melanoma cells expressing BRAF splicing variants retain exquisite sensitivity to existing FDA-approved MEK inhibitors.

References

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Nov 27, 2015·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Douglas B JohnsonDirk Schadendorf

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Citations

Jul 2, 2020·International Journal of Molecular Sciences·Anna M CzarneckaPiotr Rutkowski
Nov 9, 2018·Oncology Letters·Vivienne S LeeTimothy L Siu

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Methods Mentioned

BETA
biopsies

Software Mentioned

Human Splice Finder Tool
Human Splicing Finder system

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