MAP3K8
Overview
MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8), also known as COT or TPL2, encodes a serine/threonine kinase that activates the MAPK/ERK pathway. It has been implicated in BRAF-independent MAPK activation, making it of interest in tumors lacking canonical BRAF or NRAS mutations. In acral lentiginous melanoma (ALM), MAP3K8::DEK RNA fusions have been detected.
Alterations observed in the corpus
- MAP3K8::DEK RNA fusion detected in an integrated genomic study of acral lentiginous melanoma (34 patients; whole-genome and whole-exome sequencing with RNA-seq); one of 106 RNA fusions identified across 74% of patients (median 2 per patient); 13% of all fusions had supporting DNA breakpoints PMID:28373299
Cancer types (linked)
- ACRM (Acral Lentiginous Melanoma): MAP3K8::DEK RNA fusion identified in ALM, a UV-independent melanoma subtype with high structural variant burden and frequent TERT aberrations; specific patient count for this fusion not reported separately PMID:28373299
Co-occurrence and mutual exclusivity
- MAP3K8::DEK fusion occurs in the context of an ALM genome dominated by TERT aberrations and PAK1 copy gains; specific co-occurrence with BRAF/NRAS/NF1 driver status not reported for this fusion PMID:28373299
Therapeutic relevance
- MAP3K8 has been proposed as a target in BRAF wild-type contexts; the MAP3K8::DEK fusion in ALM may represent an alternative MAPK activation route in triple-wild-type (BRAF/NRAS/NF1 WT) tumors, but no clinical therapeutic data are reported PMID:28373299
Open questions
- Whether the MAP3K8::DEK fusion is expressed and produces a functional kinase fusion protein, and whether it confers sensitivity to MEK inhibitors, is not addressed in this study PMID:28373299
Sources
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