MED12

Overview

MED12 is a subunit of the Mediator transcriptional coactivator complex. In the corpus it appears as a recurrent alteration in alveolar rhabdomyosarcoma.

Alterations observed in the corpus

  • Recurrent alterations in extremity ARMS at 8%–17% frequency, alongside CDK4 amplifications and CDKN2A deletions PMID:37315267.
  • Recurrent alterations in fusion-positive rhabdomyosarcoma (FP-RMS) in a sequential multi-platform genomic study PMID:37730754.
  • Recurrent mutations in uterine leiomyosarcoma (ULMS, 15% frequency); infrequent in soft-tissue leiomyosarcoma (STLMS, 1%); not included in genomic risk stratification model PMID:38488807.
  • Hotspot mutations (p.G44A/D/S/R/V) more prevalent in serous endometrial carcinomas from Black patients (11% vs. 0% in White patients) PMID:37651310.
  • MED12 harbors somatic mutations in prostate cancer; identified by WES of 112 primary tumors (Broad Institute cohort) PMID:22610119
  • Novel CLL driver candidate identified in CLL WES of 160 tumors (Broad) PMID:23415222
  • Significantly mutated gene in prostate adenocarcinoma in the TCGA cohort (n=333) PMID:26544944
  • Not recurrently mutated in endometrial polyps; discussed only as comparator — MED12 is the dominant driver in uterine leiomyomas (70–80%) but was not found in this polyp cohort PMID:28445112
  • Recurrently altered candidate driver gene in medulloblastoma, stratified across subgroups in genome-wide analysis of 491 medulloblastomas PMID:28726821

Cancer types (linked)

  • ARMS — among the most common genomic events in the ARMS group of the MSKCC extremity RMS cohort (n=61) PMID:37315267.
  • Rhabdomyosarcoma (FP-RMS) — recurrent secondary alterations PMID:37730754.
  • Uterine leiomyosarcoma (ULMS) — mutated in 15%; potential biomarker for ULMS molecular classification PMID:38488807.
  • Serous endometrial carcinoma — hotspot mutations (p.G44A/D/S/R/V) enriched in Black patients (11% vs. 0%) PMID:37651310.

Co-occurrence and mutual exclusivity

  • None reported.

Therapeutic relevance

  • None reported.

Open questions

  • Whether MED12 alteration carries independent prognostic weight in ARMS is not assessed PMID:37315267.
  • The significance of MED12 hotspot mutations specifically in serous EC from Black patients is unresolved; their overlap with treatment targets requires investigation PMID:37651310.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22610119

This page was processed by crosslinker on 2026-05-14. - PMID:23415222

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

This page was processed by crosslinker on 2026-05-14. - PMID:28445112

This page was processed by wiki-cli on 2026-05-14. - PMID:28726821

This page was processed by wiki-cli on 2026-05-15.