AR amplification (high-level androgen receptor copy-number gain)
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | BIO-AR-AMPLIFICATION |
|---|---|
| Тип | Біомаркер |
| Синоніми | AR CN-ampAR HLAAR amplificationAR high-level amplificationAR ампліфікація (високорівневе підвищення копій гена рецептора андрогену)androgen receptor amplification |
| Статус | переглянуто 2026-04-29 | очікує клінічного підпису |
| Хвороби | Не вказано |
| Джерела | SRC-EAU-PROSTATE-2024 SRC-ESMO-PROSTATE-2024 SRC-NCCN-PROSTATE-2025 |
Дані про біомаркер
| Тип біомаркера | copy_number |
|---|---|
| Деталі мутації | {"functional_impact": "Increased AR protein abundance / pathway hyperactivation under castrate testosterone — drives ARSI resistance via receptor-overexpression hypersensitivity to residual androgen", "gene": "AR", "gene_hugo_id": "HGNC:644", "variant_type": "amplification"} |
| Вимірювання | MethodctDNA NGS with copy-number calling (Guardant360, FoundationOne Liquid) preferred in mCRPC; tumor-tissue NGS acceptable; FISH for AR locus (Xq12) confirmatory UnitsctDNA AR copy-number ≥2.5 (Guardant) OR tumor-tissue NGS CN-call ≥4 OR FISH AR/CEP-X ratio ≥2.0 = high-level Sensitivity requirementctDNA tumor fraction ≥1-2% required for reliable AR-CN call; low tumor fraction → false-negative. Threshold heterogeneity across assays — interpret with assay-specific cutoffs. |
| Пов’язані біомаркери | BIO-AR-V7 BIO-AR-MUTATION |
Нотатки
AR amplification is one of three dominant AR-pathway-driven ARSI-resistance mechanisms in mCRPC (alongside AR-V7 splice variant and AR ligand-binding- domain mutations). High-level AR-amp (ctDNA CN ≥2.5 by Guardant360, or tissue NGS CN ≥4) is detectable in 30-50% of mCRPC progressing on abiraterone or enzalutamide and correlates with shorter PFS/OS on continued ARSI. Distinct from AR-V7 (splice variant — see BIO-AR-V7): AR-amp = wild-type-AR overexpression (still ligand-binding-domain competent; can still respond to higher-affinity ARSI in some cases), AR-V7 = constitutively-active LBD-truncated isoform (ligand-independent, ARSI cannot bind). Clinical use: ctDNA AR-CN trajectory under ARSI monitors clonal selection; rising AR-CN signals impending progression. HOWEVER: NO FDA-approved Tx decision keyed on AR-amp; guidelines (NCCN, ESMO, EAU) treat it as informational / prognostic. Use in MDT brief to flag patients at risk of ARSI-resistance and to discuss switch to taxane (docetaxel, cabazitaxel), 177Lu-PSMA-617 (PSMA-positive), or PARPi (HRR-mutated). Trial sources for ARSI-resistance trajectory literature (PROfound exploratory ctDNA, SU2C-PCF dream-team) flagged as missing source...
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Тривожна ознака
RF-PROSTATE-AR-AMP-ARSI-RESISTANCE- AR (androgen receptor) gene amplification detected on tumor or ctDNA NGS in mCRPC — INFOR...