PTEN loss-of-function

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`BIO-PTEN`
Type	Biomarker
Aliases	PTEN lossPTEN-nullВтрата функції PTEN
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	None declared
Sources	`SRC-ESMO-BREAST-METASTATIC-2024` `SRC-NCCN-BREAST-2025` `SRC-ONCOKB`

Biomarker Facts

Biomarker type	gene_mutation
Mutation details	{"functional_impact": "Loss of PTEN phosphatase activity → unopposed PI3K signaling → AKT activation", "gene": "PTEN", "gene_hugo_id": "HGNC:9588", "hotspots": ["Frameshift / nonsense across all exons (no single hotspot)", "Biallelic loss (deletion + mutation OR two mutations OR deletion + promoter methylation)", "C-terminal truncating (loss of regulatory tail)", "R130 / R173 missense (catalytic site)"], "variant_type": "loss-of-function (frameshift / nonsense / missense / deletion)"}
Measurement	MethodDNA-NGS (mutations + copy number) PLUS PTEN IHC (loss of nuclear + cytoplasmic staining; complete or near-complete loss is the actionable readout) UnitsIHC: H-score / categorical (intact vs partial vs complete loss). NGS: variant + copy number. Sensitivity requirementIHC alone misses ~15% of biallelic-LOF cases → combine with NGS for actionability decisions (e.g. CAPItello-291 enrolment criteria)
Related biomarkers	`BIO-PIK3CA-MUTATION` `BIO-AKT1`

Notes

Endometrial: ~75% (most common single mutation in EC). Glioma: ~40% in GBM. Prostate: ~20% with biallelic loss in metastatic castration-resistant disease (worse prognosis). Breast: ~5–10%. Capivasertib + fulvestrant (CAPItello-291) approved for HR+ HER2− advanced breast with PIK3CA / AKT1 / PTEN alteration after CDK4/6i progression — PTEN-loss subgroup benefited. Ipatasertib + abiraterone in mCRPC (IPATential150) showed PFS benefit in PTEN-loss subgroup (FDA review pending). Definition of "PTEN loss" varies across trials — IHC + NGS combined is the most consistent operational definition.

Used By

Biomarker

BIO-AKT1 - AKT1 E17K mutation
BIO-PIK3R1 - PIK3R1 mutation (p85α regulatory subunit of PI3K)

Indications

IND-BREAST-HR-POS-2L-AKT-CAPIVASERTIB - IND-BREAST-HR-POS-2L-AKT-CAPIVASERTIB

Questionnaires

QUEST-BREAST-1L-STUB - Invasive breast cancer — first line