PPP2R2A
Overview
PPP2R2A encodes the B55-alpha regulatory subunit of PP2A (Protein Phosphatase 2A), a mitotic exit phosphatase complex. PP2A-B55 dephosphorylates CDK1 substrates during mitotic exit, and its loss may impair proper cell cycle control. Heterozygous and homozygous deletions of PPP2R2A in breast cancer, particularly in mitotic ER-positive (luminal B) tumors, support a tumor suppressor role in regulating the G2/M transition.
Alterations observed in the corpus
- PPP2R2A (8p21) heterozygous and homozygous deletions drive loss of expression in mitotic ER-positive (luminal B) breast cancers in the METABRIC cohort (~2,000 tumors); identified as a putative tumor suppressor by CNA-expression outlier analysis PMID:22522925
Cancer types (linked)
- BRCA (Breast cancer): Homozygous and heterozygous deletions enriched in luminal B (ER-positive, high proliferation) breast cancer; loss confirmed by cis-acting expression change PMID:22522925
Co-occurrence and mutual exclusivity
- Deletions enriched in the mitotic ER-positive (luminal B) IntClust subtypes within METABRIC PMID:22522925
Therapeutic relevance
- PP2A is a serine/threonine phosphatase complex with broad tumor suppressor functions; PPP2R2A loss may sensitize tumors to CDK inhibitors by maintaining aberrant CDK substrate phosphorylation, though this is speculative and not addressed in the corpus.
Open questions
- Whether PPP2R2A loss is an independent driver or co-selected with other 8p21 locus deletions (e.g., NKX3-1 in prostate cancer) remains to be determined in breast cancer.
Sources
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