MAPK1

Overview

MAPK1 (also known as ERK2) is a central kinase in the RAS/MAPK signaling cascade. Alterations in MAPK1 can activate downstream proliferative signaling. In the context of BRAF fusions, co-mutations in MAPK pathway genes such as MSH3 have been identified in BRAF fusion-positive colorectal cancer.

Alterations observed in the corpus

  • MSH3 (not MAPK1 directly) was identified as a frequent co-mutation in BRAF fusion-positive colorectal cancers, along with RNF43, KMT2D, and ARID1A; MAPK pathway activation is a central mechanistic theme of BRAF fusions across 52 histologies PMID:38922339.
  • Alterations in near haploid ALL contributing to RTK/Ras pathway activation (70.6% of near haploid cases with combined RTK/Ras alterations; St. Jude, 44 tumors) PMID:23334668
  • CRKL–MAPK1 singleton sense-preserving fusion detected in prostate tumor P04-1084 via chromoplexy; MAPK1 kinase domain intact in fusion product, hypothesized to drive aberrant ERK2 kinase activity PMID:23622249
  • Phospho-ERK1/2 (T202/Y204, MAPK1/MAPK3) highest in RAS-mutant melanoma subtype by RPPA in the TCGA 333-sample cutaneous melanoma cohort; reflects hyperactivation of MAPK signalling in NRAS/HRAS/KRAS-mutant tumours PMID:26091043
  • Recurrent E322 mutations (p.Glu322Ala, p.Glu322Lys) in CTCL/Sézary syndrome exome cohort; E322K is a previously reported activating allele validated to drive ERK1/2 hyperactivation PMID:26551667
  • MAPK1 (ERK2) amplification raises the proportion of lung ADCs with a candidate Ras/Raf/RTK pathway driver to 76% in pan-lung cancer TCGA analysis (n=1144) PMID:27158780
  • Mutation in a recurrent/metastatic head and neck cancer patient guided treatment with an ERK inhibitor on a single-patient IND basis PMID:27442865

Cancer types (linked)

  • BRAF fusion-positive cancers (multiple histologies) — MAPK pathway activation via constitutive BRAF dimerization is the unifying oncogenic mechanism PMID:38922339.

Co-occurrence and mutual exclusivity

  • Not specifically reported in the corpus for MAPK1 itself; co-mutations in MAPK pathway context include MSH3, RNF43, KMT2D in colorectal BRAF fusion-positive cases PMID:38922339.

Therapeutic relevance

Open questions

  • Whether direct MAPK1 alterations contribute to BRAF fusion-driven tumors beyond the general pathway activation is not characterized in the corpus.

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:23334668

This page was processed by entity-page-writer on 2026-05-15. - PMID:23622249

This page was processed by entity-page-writer on 2026-05-15. - PMID:26091043

This page was processed by entity-page-writer on 2026-05-15. - PMID:26551667

This page was processed by entity-page-writer on 2026-05-15. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:27442865

This page was processed by entity-page-writer on 2026-05-15.