Mutação PIK3R1 (subunidade regulatória p85α de PI3K)
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| ID | BIO-PIK3R1 |
|---|---|
| Tipo | Biomarcador |
| Alegais | Mutação PIK3R1 / p85αМутація PIK3R1 (регуляторна субодиниця p85α PI3K) |
| Estado | reviewed 2026-05-04 | pending_clinical_signoff |
| Doenças | DIS-ENDOMETRIAL |
| Fontes | SRC-ESGO-ENDOMETRIAL-2025 SRC-NCCN-UTERINE-2025 |
Fatos de biomarcadores
| Tipo de biomarcador | gene_mutation |
|---|---|
| Detalhes da mutação | {"exon": "multiple (iSH2 domain, nSH2 domain: codons 449–580 most common)", "functional_impact": "activating (via reduced inhibitory constraint on PI3Kα catalytic subunit p110α)", "gene": "PIK3R1", "variant_type": "loss-of-function or gain-of-function (heterogeneous; iSH2 domain deletions → reduced p85α inhibition of p110α → PI3K activation)"} |
| Medição | MétodoPainel NGS tumoral; comumente co-testado com PIK3CA |
| Procura de ação | {"gene": "PIK3R1", "variant": "activating_mutation"} |
| Biomarcadores relacionados | BIO-PIK3CA BIO-PTEN |
Notas
PIK3R1 encodes the p85α regulatory subunit of PI3Kα (phosphatidylinositol 3-kinase). p85α normally inhibits the p110α catalytic subunit; PIK3R1 mutations (deletions and missense in the iSH2 domain) reduce this inhibition, activating PI3K/AKT/mTOR signaling. Clinical contexts: (1) Endometrial cancer: PIK3R1 mutations in ~33% — among the highest frequencies in any cancer type. Co-occurs with PIK3CA (~50% of EC have PI3K pathway mutations). PIK3R1-mutant EC may be sensitized to PI3K/AKT/mTOR inhibitors. Alpelisib (PI3Kα inhibitor) is FDA-approved for PIK3CA-mutant HR+ breast cancer (SOLAR-1); evidence in EC is more limited — lenvatinib + everolimus is the approved mTOR-based combination for advanced EC (KEYNOTE-775, not PIK3R1-specific). Copanlisib (pan-PI3K inhibitor) and other PI3K inhibitors are being evaluated in EC basket trials. (2) Breast cancer: PIK3R1 mutations in ~8–10% (often with PIK3CA co-mutation); may predict PI3K inhibitor sensitivity similarly to PIK3CA. (3) Glioblastoma: PIK3R1 mutations in ~10%. Therapeutic note: alpelisib (PI3Kα-specific) is approved only for PIK3CA-mutant HR+ breast cancer (companion diagnostic: therascreen PIK3CA test). PIK3R1 mutations are not...
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