RB1 loss-of-function (retinoblastoma protein)
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | BIO-RB1 |
|---|---|
| Тип | Біомаркер |
| Синоніми | RB1 loss / retinoblastoma gene mutationВтрата функції RB1 (ретинобластомний білок) |
| Статус | переглянуто 2026-05-04 | очікує клінічного підпису |
| Хвороби | Не вказано |
| Джерела | SRC-EAU-BLADDER-2024 SRC-NCCN-SCLC-2025 |
Дані про біомаркер
| Тип біомаркера | gene_mutation |
|---|---|
| Деталі мутації | {"exon": "multiple (exons 1–27)", "functional_impact": "loss-of-function", "gene": "RB1", "variant_type": "loss-of-function (deletion, frameshift, nonsense, splice, missense inactivating)"} |
| Вимірювання | MethodTumor NGS; IHC (Rb protein loss by IHC — used clinically in SCLC diagnosis); FISH for 13q14 deletion (retinoblastoma) |
| Пошук клінічної застосовності | {"gene": "RB1", "variant": "loss_of_function"} |
| Пов’язані біомаркери | BIO-CDKN2A |
Нотатки
RB1 encodes the retinoblastoma protein (pRb), the master G1/S checkpoint regulator. pRb normally sequesters E2F transcription factors to prevent S-phase entry; loss of pRb → uncontrolled cell cycle progression. Clinical contexts: (1) Hereditary retinoblastoma: germline RB1 mutation → bilateral/multifocal retinoblastoma in childhood; lifetime elevated risk of osteosarcoma, SCLC, melanoma. (2) SCLC: biallelic RB1 loss + TP53 mutation defines the SCLC molecular signature (~95% of SCLC). pRb loss by IHC is used in pathologic diagnosis. No targeted therapy for RB1 deficiency per se; SCLC treatment is chemotherapy (EP/EC) ± atezolizumab. (3) Urothelial carcinoma: RB1 alterations in ~30% of muscle-invasive bladder cancer; associated with basal/squamous subtype; not currently targeted. (4) Breast cancer: RB1 mutations occur in ~10% of TNBC; RB1 loss predicts resistance to CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) — pRb is the substrate for CDK4/6 that drives cell cycle entry; without pRb, CDK4/6 inhibition is ineffective. (5) Osteosarcoma: RB1 alterations in ~30%. Therapeutic implication of RB1 loss in HR+ breast cancer: CDK4/6 inhibitors are essentially non-functional with...
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Клінічна застосовність
BMA-RB1-SCLC- RB1 biallelic loss, together with TP53 loss, is the molecular hallmark of SCLC (~95% of c...BMA-RB1-UROTHELIAL- RB1 alterations (deletion, mutation) occur in ~30% of muscle-invasive bladder cancer (MIB...