NRG1 fusion (gene rearrangement)
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | BIO-NRG1-FUSION |
|---|---|
| Тип | Біомаркер |
| Синоніми | ATP1B1-NRG1CD74-NRG1NRG1 fusionNRG1 rearrangementSLC3A2-NRG1neuregulin-1 fusionПеребудова / фузія NRG1 |
| Статус | переглянуто 2026-04-29 | очікує клінічного підпису |
| Хвороби | Не вказано |
| Джерела | SRC-CIVIC SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 |
Дані про біомаркер
| Тип біомаркера | gene_fusion |
|---|---|
| Деталі мутації | {"functional_impact": "Aberrant NRG1 (neuregulin-1) ligand expression on tumor cell surface → paracrine / autocrine ERBB3 (HER3) activation → ERBB2-ERBB3 heterodimer signalling. Driver event in fusion-positive tumors; targetable by HER2 + HER3 dual blockade (zenocutuzumab).\n", "gene": "NRG1", "gene_hugo_id": "HGNC:7997", "hgvs_coding": "", "hgvs_protein": "", "variant_type": "fusion"} |
| Вимірювання | MethodRNA-based NGS (preferred — DNA panels miss many breakpoints because NRG1 introns are very large). Targeted RNA fusion panels OR whole-transcriptome RNA-seq. FISH break-apart possible but lower sensitivity. IHC for HER3 activation is not specific. Unitscategorical (positive | negative) Sensitivity requirementRNA-NGS recommended; DNA-only panels report 30-40% false-negative rate for NRG1 fusions due to breakpoint variability and large intron size. |
| Пов’язані біомаркери | BIO-ALK-FUSION BIO-ROS1 BIO-RET-FUSION |
Нотатки
Rare but tumor-agnostic actionable driver. Highest prevalence in invasive mucinous adenocarcinoma of lung (~7-27% of KRAS-WT IMA), pancreatic KRAS-WT (~3-5%), and isolated cholangio / breast / sarcoma cases. Zenocutuzumab (Bizengri, MCLA-128) — first-in-class HER2 × HER3 bispecific IgG1 — granted FDA accelerated approval 4 Dec 2024 for advanced unresectable / metastatic NSCLC and pancreatic cancer with NRG1 fusion who progressed on prior systemic therapy. eNRGy phase-2 trial (n=204): ORR 33% NSCLC, 42% pancreatic; mDOR ~7-9 mo. Pan-tumor approval reflects rarity (no head-to-head alternative). RNA-NGS testing critical — fusion missed by DNA-only panels in 30-40% of cases. Clinical practice gap: most KRAS-WT pancreatic / IMA-NSCLC patients still not tested at progression. Trial-Source SRC-ENRGY-SCHRAM-2024 not yet ingested — flag for ingestion chunk.
Де використовується
Indications
IND-NSCLC-NRG1-ZENOCUTUZUMAB- IND-NSCLC-NRG1-ZENOCUTUZUMAB
Клінічна застосовність
BMA-NRG1-FUSION-NSCLC- NRG1 fusions (~0.2% NSCLC; enriched in invasive mucinous adenocarcinoma, never-smokers) d...BMA-NRG1-FUSION-PDAC- NRG1 fusions occur in ~0.5% of pancreatic ductal adenocarcinoma (PDAC) — a rare but actio...