Concomitant BCORL1 and BRAF Mutations in Vemurafenib-Resistant Melanoma Cells.

ABSTRACT: BRAF is the most frequently mutated gene in melanoma. Constitutive activation of mutant BRAF^V600E leads to aberrant Ras-independent MAPK signaling and cell transformation. Inhibition of mutant BRAF is a current frontline therapy for such cases, with improved survival compared with chemotherapy. Unfortunately, reactivation of MAPK signaling by several mechanisms has been shown to cause drug resistance and disease recurrence. In this work, we describe the co-occurrence of an in-frame deletion within an amplified BRAF^V600E locus and a missense point mutation of the transcriptional repressor BCORL1 in vemurafenib-resistant A375 melanoma cells. Functional data confirmed that truncated p47BRAF^V600E and mutant BCORL1^Q1076H both contribute to resistance.

SUBMITTER: Mologni L 

PROVIDER: S-EPMC5915992 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature