{"entity":{"id":"cdkn2a-homozygous-deletion","kind":"term","name":"CDKN2A/B homozygous deletion","aka":["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"],"tldr":"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.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/CDKN2A","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CDKN2A"}],"tags":[],"related":["prmt5-mtap","cdk4-6","fish","cns-tumour-methylation-classifier","1p19q-codeletion","bap1-loss","hereditary-cancer-syndromes","ihc"],"cancers":["idh-mutant-astrocytoma","oligodendroglioma","glioblastoma","meningioma","pleural-mesothelioma","peritoneal-mesothelioma","paediatric-low-grade-glioma","paediatric-high-grade-glioma","malignant-peripheral-nerve-sheath-tumour","myxofibrosarcoma","ewing-sarcoma","richter-transformation-cll","papillary-rcc","undifferentiated-pleomorphic-sarcoma","hpv-negative-head-and-neck-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/cdkn2a-homozygous-deletion/","neighbours":{"target":[{"id":"cdk4-6","kind":"target","name":"CDK4/6","route":"/targets/cdk4-6/"},{"id":"prmt5-mtap","kind":"target","name":"PRMT5 (MTAP-deleted cancers)","route":"/targets/prmt5-mtap/"}],"term":[{"id":"1p19q-codeletion","kind":"term","name":"1p/19q codeletion","route":"/terms/1p19q-codeletion/"},{"id":"bap1-loss","kind":"term","name":"BAP1 loss","route":"/terms/bap1-loss/"},{"id":"ependymoma-molecular-groups","kind":"term","name":"Ependymoma molecular groups (PF-A, PF-B, ZFTA, YAP1, MYCN)","route":"/terms/ependymoma-molecular-groups/"},{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"hereditary-cancer-syndromes","kind":"term","name":"Hereditary cancer syndromes","route":"/terms/hereditary-cancer-syndromes/"},{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"}],"technology":[{"id":"cns-tumour-methylation-classifier","kind":"technology","name":"Methylation classifier for brain tumours","route":"/technologies/cns-tumour-methylation-classifier/"}],"cancer":[{"id":"idh-mutant-astrocytoma","kind":"cancer","name":"Astrocytoma, IDH-mutant (grades 2 to 4)","route":"/cancers/idh-mutant-astrocytoma/"},{"id":"ewing-sarcoma","kind":"cancer","name":"Ewing sarcoma","route":"/cancers/ewing-sarcoma/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"},{"id":"hpv-negative-head-and-neck-cancer","kind":"cancer","name":"HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)","route":"/cancers/hpv-negative-head-and-neck-cancer/"},{"id":"malignant-peripheral-nerve-sheath-tumour","kind":"cancer","name":"Malignant peripheral nerve sheath tumour (MPNST)","route":"/cancers/malignant-peripheral-nerve-sheath-tumour/"},{"id":"meningioma","kind":"cancer","name":"Meningioma","route":"/cancers/meningioma/"},{"id":"myxofibrosarcoma","kind":"cancer","name":"Myxofibrosarcoma","route":"/cancers/myxofibrosarcoma/"},{"id":"oligodendroglioma","kind":"cancer","name":"Oligodendroglioma, IDH-mutant and 1p/19q-codeleted","route":"/cancers/oligodendroglioma/"},{"id":"oral-tongue-cancer","kind":"cancer","name":"Oral tongue and floor of mouth cancer","route":"/cancers/oral-tongue-cancer/"},{"id":"paediatric-high-grade-glioma","kind":"cancer","name":"Paediatric high-grade glioma (excluding diffuse midline glioma)","route":"/cancers/paediatric-high-grade-glioma/"},{"id":"paediatric-low-grade-glioma","kind":"cancer","name":"Paediatric low-grade glioma","route":"/cancers/paediatric-low-grade-glioma/"},{"id":"papillary-rcc","kind":"cancer","name":"Papillary renal cell carcinoma","route":"/cancers/papillary-rcc/"},{"id":"peritoneal-mesothelioma","kind":"cancer","name":"Peritoneal mesothelioma","route":"/cancers/peritoneal-mesothelioma/"},{"id":"pleural-mesothelioma","kind":"cancer","name":"Pleural mesothelioma","route":"/cancers/pleural-mesothelioma/"},{"id":"richter-transformation-cll","kind":"cancer","name":"Richter transformation of chronic lymphocytic leukaemia","route":"/cancers/richter-transformation-cll/"},{"id":"undifferentiated-pleomorphic-sarcoma","kind":"cancer","name":"Undifferentiated pleomorphic sarcoma (UPS)","route":"/cancers/undifferentiated-pleomorphic-sarcoma/"}]}}