PPP2R1A

Overview

PPP2R1A encodes the scaffold A subunit of Protein Phosphatase 2A (PP2A), a serine/threonine phosphatase that negatively regulates the PI3K/AKT/mTOR and RAS/MAPK pathways. Mutations in PPP2R1A disrupt PP2A tumor-suppressor activity and are recurrent in endometrial carcinoma, particularly in the copy-number high/TP53-abnormal (CN-H/TP53abn) subtype.

Alterations observed in the corpus

  • PPP2R1A mutations were less frequent in CN-H/TP53abn endometrial carcinomas from Black patients compared to White patients (15% vs. 28%), consistent with the overall shift away from endometrioid-associated PI3K pathway alterations in the Black EC population PMID:37651310.
  • Mutated in 22% of copy-number-high serous-like endometrial tumors (Q=1.7×10⁻¹⁶); previously noted as a serous-specific driver PMID:23636398
  • M180R HEAT-domain hotspot mutation in 1 uterine carcinosarcoma case PMID:25233892
  • Recurrent low-VAF oncogenic mutations in endometrial polyps (WGS, 23 polyps); part of the canonical UCEC driver gene landscape co-occurring with PIK3CA, PIK3R1, PTEN, ERBB2, and FBXW7 mutations PMID:28445112
  • Mutated in 15.9% of clear-cell endometrial carcinoma (CCEC; n=63); co-enriched with TP53 in serous-like profiles, suggesting a role in high-grade CCEC PMID:28485815
  • Referenced from prior targeted-panel literature as recurrent in HPV(−) vulvar SCC; not identified as a new finding in this 15-tumor WES cohort PMID:29422544

Cancer types (linked)

  • Endometrial carcinoma (UCEC) — PPP2R1A mutations enriched in the CN-H/TP53abn molecular subtype; less prevalent in Black patients (15% vs. 28%) PMID:37651310.

Co-occurrence and mutual exclusivity

  • PPP2R1A mutations co-occur with the CN-H/TP53abn molecular subtype of endometrial carcinoma; they are inversely related to the endometrioid-enriched molecular class PMID:37651310.

Therapeutic relevance

  • Lower prevalence of PPP2R1A mutations in Black EC patients reduces their representation in the PI3K/AKT/mTOR-pathway-altered subgroup; this may affect eligibility for mTOR inhibitor trials PMID:37651310.

Open questions

  • Whether PPP2R1A mutations specifically define a targetable PP2A-loss EC subtype amenable to specific therapeutic combinations (e.g., mTOR + AKT inhibition) is not established in the corpus.

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:29422544

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