Table 3 The presence and role of specific SVs
Transcript | Splicing event | Functional role | Molecular mechanism |
|---|---|---|---|
BRAF | Skipping of the BRAF V600E exons 4–8 | Resistance to vemurafenib | Missing the RAS-binding domain (RBD) |
NRAS | Isoform 1 (canonical) | Resistance to vemurafenib Potentially serve as biomarkers for therapeutic response and disease prognosis | Lower activity of MEK and ERK and a level of activity |
Isoform 2 (insert exon3b) | Caused less activity along the MEK/ERK axis and increased activity of AKT | ||
Isoform 3(skipping of exon 3) | Lower activity of MEK and ERK and a level of activity | ||
Isoform 4(skipping of exons 3 and 4) | Lower activity of MEK and ERK and a level of activity | ||
Isoform 5(the fusion of the beginning of exon 2 with the end of exon 5) | Increased the activity of all downstream targets | ||
BCL-2 Family | Bcl-xL(alternative 5’ splice site selection within exon 2) | Confer chemo-resistance | Binding the BH4 domain in the N-terminal |
Mcl-1 L & Mcl-1 S | Induced apoptosis | Targeting Mcl-1 pre-mRNA with Mcl-1 antisense morpholino oligonucleotides resulted in a shift towards Mcl-1 S expression | |
BimS, BimL & BimEL | Induced apoptosis of BRAFV600E melanoma | Unknown | |
MDM4 | MDM4-S(skipping of exon 6) | Increased sensitivity to cytotoxic chemotherapy and to inhibitors of the BRAF (V600E) oncogene | A negative regulator of p53 |
CD44 | CD44v8-10 | related to melanoma metastasis | Regulated by CD82-U2AF2 axis |