The landscape of BRAF transcript and protein variants in human cancer

摘要: The BRAF protein kinase is widely studied as a cancer driver and therapeutic target. However, the regulation of its expression not completely understood. Taking advantage RNA-seq data more than 4800 patients belonging to 9 different types, we show that mRNA exists pool 3 isoforms (reference BRAF, BRAF-X1, BRAF-X2) differ in last part their coding sequences, well length (BRAF-ref: 76 nt; BRAF-X1 BRAF-X2: up 7 kb) sequence 3’UTRs. levels BRAF-ref BRAF-X1/X2 are inversely correlated, while most prevalent among three varies from type type. In melanoma cells, X1 isoform expressed at highest level both therapy-naive cells with acquired resistance vemurafenib driven by gene amplification or Δ[3–10] splicing variant. addition protein, (the full variant) also translated. proteins similar, together they account for functional activities. contrast, endogenous BRAF-X2 hard detect because C-terminal domain selectively recognized ubiquitin-proteasome pathway targeted degradation. By shedding light on repertoire variants, complex expression, our work paves way deeper understanding crucially important player human informed development new strategies.