CDKN2A loss (homozygous deletion or biallelic inactivation)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-CDKN2A |
|---|---|
| Type | Biomarker |
| Aliases | 9p21 deletionCDKN2A lossp14ARF lossp16 lossВтрата CDKN2A (гомозиготна делеція або біалельна інактивація) |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-MELANOMA-2025 SRC-ONCOKB |
Biomarker Facts
| Biomarker type | copy_number |
|---|---|
| Mutation details | {"functional_impact": "Loss of p16(INK4a) tumor-suppressor (CDK4/6 inhibition lost — Rb constitutively phosphorylated) and loss of p14(ARF) (MDM2 destabilization of p53 lost)", "gene": "CDKN2A", "gene_hugo_id": "HGNC:1787", "hotspots": ["Homozygous deletion (9p21.3 — most common mechanism)", "Biallelic inactivation: deletion + mutation", "Promoter hypermethylation (silencing without copy loss)"], "variant_type": "deletion / loss-of-function"} |
| Measurement | MethodDNA-NGS with copy-number module (preferred) OR FISH (9p21) OR p16 IHC (loss correlates with biallelic inactivation) UnitsCopy number (0 = homozygous deletion, 1 = heterozygous loss, 2 = neutral) Sensitivity requirementTumor cellularity ≥30% recommended for copy-number calling on DNA-NGS |
| Related biomarkers | BIO-TP53-MUTATION |
Notes
~50% of melanoma, ~50% of squamous NSCLC, ~80% of MPNST, ~50% of glioblastoma, ~30% of pancreatic. Marker of poor prognosis across many tumors. No directly approved targeted agent — CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) are biologically rational (synthetic-lethal hypothesis: loss of p16 → reliance on CDK4/6) but no large positive trial in solid tumors outside HR+ breast. Selective CDK7 / PRMT5 inhibitors in development for MTAP-codeleted (9p21 co-deletion) tumors. In MPNST, CDKN2A loss is near-universal in malignant transformation from neurofibroma.
Used By
Biomarker
BIO-1P19Q-CODELETION- 1p/19q codeletionBIO-ATRX-MUTATION- ATRX mutation / ATRX loss (IHC)BIO-FBXW7- FBXW7 loss-of-function mutationBIO-RB1- RB1 loss-of-function (retinoblastoma protein)BIO-TERT- TERT promoter mutation (C228T / C250T)
Diseases
DIS-CHONDROSARCOMA- ChondrosarcomaDIS-GLIOMA-LOW-GRADE- Low-grade glioma (LGG, WHO grade 2 — IDH-mutant)DIS-MASTOCYTOSIS- Advanced systemic mastocytosis (AdvSM)DIS-MPNST- Malignant peripheral nerve sheath tumor (MPNST)
Red flag
RF-CHONDROSARCOMA-HIGH-RISK-BIOLOGY- Adverse subtype or molecular feature in chondrosarcoma: dedifferentiated subtype (high-gr...RF-MPNST-HIGH-RISK-BIOLOGY- MPNST with adverse molecular / clinical features: biallelic CDKN2A/B loss (>80% high-grad...