# CDKN2A/B homozygous deletion

Source: https://onco.cc/terms/cdkn2a-homozygous-deletion/  
OnCo record `cdkn2a-homozygous-deletion` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Losing both copies of the CDKN2A/B genes on chromosome 9p21 removes the cell's main brake on division; in an IDH-mutant glioma it alone makes the tumour grade 4, in mesothelioma and melanoma it marks aggressive disease, and the neighbouring MTAP gene usually goes with it, opening a new drug target.

## Summary

What is measured: biallelic loss of the CDKN2A and CDKN2B tumour suppressors at 9p21, which encode p16, p14ARF and p15. How: FISH with a 9p21 probe (also on effusion cytology in mesothelioma), copy-number from methylation or SNP arrays, next-generation sequencing copy-number calls, or MTAP immunohistochemistry as a surrogate because MTAP is co-deleted in 80 to 90 percent; p16 immunohistochemistry loss is less specific. Frequencies: 15 to 20 percent of IDH-mutant astrocytomas (grade 4 by definition in WHO 2021 whatever the histology), a defining feature of grade 3 meningioma, about 45 percent of mesotheliomas, most pancreatic cancers, many melanomas and sarcomas; germline CDKN2A causes familial melanoma. What a positive result changes: in glioma it assigns grade 4 and full radiotherapy with temozolomide, and excludes the patient from de-escalation; in meningioma it assigns grade 3 and radiotherapy; in mesothelioma it separates malignancy from reactive mesothelial proliferation; MTAP co-deletion opens trials of PRMT5 inhibitors (MRTX1719, AMG 193) and MAT2A inhibitors; CDK4/6 inhibitor trials have shown only modest activity. Where it matters: IDH-mutant astrocytoma, oligodendroglioma, glioblastoma, meningioma, paediatric gliomas, mesothelioma, HPV-negative head and neck cancer, MPNST, sarcomas, papillary RCC and Richter transformation.

## Fields

- Kind: Term
- Last checked: 2026-09-17
- Also known as: CDKN2A; CDKN2A deletion; CDKN2A loss; CDKN2A/B deletion; CDKN2A/B homozygous deletion; 9p21 deletion; 9p21 loss; p16 loss; MTAP deletion; CDKN2A/MTAP deletion; MTAP loss; MTAP-deleted; CDKN2A-deleted

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/CDKN2A
- Wikipedia: https://en.wikipedia.org/wiki/CDKN2A

## Connected records

- targets: [CDK4/6](https://onco.cc/targets/cdk4-6/), [PRMT5 (MTAP-deleted cancers)](https://onco.cc/targets/prmt5-mtap/)
- terms: [1p/19q codeletion](https://onco.cc/terms/1p19q-codeletion/), [BAP1 loss](https://onco.cc/terms/bap1-loss/), [Ependymoma molecular groups (PF-A, PF-B, ZFTA, YAP1, MYCN)](https://onco.cc/terms/ependymoma-molecular-groups/), [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- technologies: [Methylation classifier for brain tumours](https://onco.cc/technologies/cns-tumour-methylation-classifier/)
- cancers: [Astrocytoma, IDH-mutant (grades 2 to 4)](https://onco.cc/cancers/idh-mutant-astrocytoma/), [Ewing sarcoma](https://onco.cc/cancers/ewing-sarcoma/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)](https://onco.cc/cancers/hpv-negative-head-and-neck-cancer/), [Malignant peripheral nerve sheath tumour (MPNST)](https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/), [Meningioma](https://onco.cc/cancers/meningioma/), [Myxofibrosarcoma](https://onco.cc/cancers/myxofibrosarcoma/), [Oligodendroglioma, IDH-mutant and 1p/19q-codeleted](https://onco.cc/cancers/oligodendroglioma/), [Oral tongue and floor of mouth cancer](https://onco.cc/cancers/oral-tongue-cancer/), [Paediatric high-grade glioma (excluding diffuse midline glioma)](https://onco.cc/cancers/paediatric-high-grade-glioma/), [Paediatric low-grade glioma](https://onco.cc/cancers/paediatric-low-grade-glioma/), [Papillary renal cell carcinoma](https://onco.cc/cancers/papillary-rcc/), [Peritoneal mesothelioma](https://onco.cc/cancers/peritoneal-mesothelioma/), [Pleural mesothelioma](https://onco.cc/cancers/pleural-mesothelioma/), [Richter transformation of chronic lymphocytic leukaemia](https://onco.cc/cancers/richter-transformation-cll/), [Undifferentiated pleomorphic sarcoma (UPS)](https://onco.cc/cancers/undifferentiated-pleomorphic-sarcoma/)

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