ARAF
Overview
ARAF (A-Raf proto-oncogene, serine/threonine kinase) is a member of the RAF kinase family involved in MAPK/ERK signaling. Unlike BRAF and CRAF (RAF1), ARAF is less commonly altered in cancer but has been identified as a subclonal somatic mutation in rare tumor types including breast adenoid cystic carcinoma (AdCC).
Alterations observed in the corpus
- Subclonal missense mutation in at least one breast adenoid cystic carcinoma (AdCC) case; identified as a non-passenger event in a WES cohort of 12 breast AdCCs; associated with intra-tumor heterogeneity at diagnosis PMID:26095796
- 2 hotspot S214Y/S214P missense mutations in LUAD (MSK-IMPACT cohort, n=860); S214 alleles are sorafenib-sensitive in prior preclinical work PMID:28336552
Cancer types (linked)
- ACBC / BRCA: subclonal ARAF mutation in breast AdCC; tumor carries recurrent MYB-NFIB fusion and low overall mutation rate (0.27 non-silent mutations/Mb) PMID:26095796
Co-occurrence and mutual exclusivity
- Occurs in the context of MYB-NFIB fusion-positive breast AdCCs; co-occurs with other subclonal drivers (FBXW7, MTOR, KMT2D, CDH1) suggesting polyclonal architecture PMID:26095796
Therapeutic relevance
- Authors note that subclonal driver mutations including ARAF may underlie therapeutic escape; no specific ARAF-directed therapeutics tested in this study PMID:26095796
Open questions
- Clinical significance of subclonal ARAF mutations in low-instability, indolent breast AdCC tumors remains to be elucidated PMID:26095796
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:28336552
This page was processed by wiki-cli on 2026-05-14.