POLR2A

Overview

POLR2A encodes the largest subunit of RNA polymerase II, the enzyme responsible for mRNA transcription. Rare point mutations in POLR2A have been identified as driver events in the NF2-wildtype (MG2) molecular group of meningiomas, suggesting that transcriptional dysregulation contributes to a subset of benign meningiomas.

Alterations observed in the corpus

  • POLR2A point mutations are exclusive to the MG2 (benign NF2-wildtype) molecular group of meningiomas, occurring in 6% of MG2 tumors; they are not observed in NF2-mutant meningioma groups PMID:34433969.
  • Harbored deleterious mutations in ≥4 DCB patients and 0 NDB patients in a pembrolizumab NSCLC cohort; association not corrected for overall mutation burden and requires independent validation PMID:25765070

Cancer types (linked)

  • Meningioma (MNG) — POLR2A mutations restricted to the NF2-wildtype MG2 molecular group (6%); co-occur with other MG2-exclusive drivers TRAF7, AKT1, KLF4, SMO PMID:34433969.

Co-occurrence and mutual exclusivity

  • POLR2A mutations are mutually exclusive with NF2 mutations in meningioma; they co-occur with other MG2 drivers including TRAF7 (25%), AKT1 (13%), KLF4 (13%), and SMO mutations PMID:34433969.

Therapeutic relevance

  • MG2 tumors (benign NF2-wildtype) harboring POLR2A and related MG2 mutations have favorable prognosis; targeted therapies directed at the specific co-occurring pathway alterations (e.g., AKT1/SMO inhibitors) may be relevant PMID:34433969.

Open questions

  • The specific mechanism by which POLR2A mutations drive MG2 meningioma biology is not established; whether these mutations alter transcriptional programs for specific oncogenes or tumor suppressors is unknown.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:25765070

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