{"entity":{"id":"tp53-mutated","kind":"term","name":"TP53-mutated (p53-abnormal)","aka":["TP53-mutated","TP53-mutant","TP53 mutation","TP53 mutations","TP53 loss","TP53-altered","p53abn","p53-abnormal","p53 abnormal","p53-mutant","mutant p53","TP53/RB1","TP53 and RB1","multi-hit TP53"],"tldr":"Loss of the p53 'guardian of the genome', the most commonly mutated gene in cancer. In blood cancers and several solid tumours a TP53 mutation marks the highest-risk group, resistant to chemotherapy and hard to treat.","summary":"TP53 is mutated in about half of all cancers and in almost all high-grade serous ovarian and small-cell lung cancers. Where it is variable it defines risk: TP53-mutated AML and MDS (especially multi-hit) have median survivals under a year and are excluded from many trials; del(17p)/TP53 CLL is treated with BTK inhibitors rather than chemoimmunotherapy; p53-abnormal endometrial cancer (by immunohistochemistry) is the aggressive molecular class that benefits from chemotherapy and trastuzumab if HER2-positive; TP53 and RB1 co-loss in prostate and lung adenocarcinoma predicts neuroendocrine transformation. Restoring p53 (eprenetapopt, MDM2 inhibitors for wild-type tumours) has so far disappointed.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/P53","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/P53"}],"tags":[],"related":["wild-type","cytogenetics","li-fraumeni"],"cancers":["aml","cll","endometrial","ovarian"],"sections":["diagnostics"],"technologies":[],"targets":["tp53","mdm2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/tp53-mutated/","neighbours":{"term":[{"id":"aml-myelodysplasia-related","kind":"term","name":"AML with myelodysplasia-related gene mutations (AML-MR)","route":"/terms/aml-myelodysplasia-related/"},{"id":"cytogenetics","kind":"term","name":"Cytogenetics and karyotype","route":"/terms/cytogenetics/"},{"id":"del5q","kind":"term","name":"del(5q) (5q- syndrome and lenalidomide response)","route":"/terms/del5q/"},{"id":"foxo1-fusion-status","kind":"term","name":"FOXO1 fusion status and IRS group (rhabdomyosarcoma)","route":"/terms/foxo1-fusion-status/"},{"id":"ipss-m-ipss-r","kind":"term","name":"IPSS-R and IPSS-M (myelodysplastic syndrome risk scores)","route":"/terms/ipss-m-ipss-r/"},{"id":"li-fraumeni","kind":"term","name":"Li-Fraumeni syndrome (germline TP53)","route":"/terms/li-fraumeni/"},{"id":"medulloblastoma-molecular-groups","kind":"term","name":"Medulloblastoma molecular groups (WNT, SHH, group 3, group 4)","route":"/terms/medulloblastoma-molecular-groups/"},{"id":"mipi","kind":"term","name":"MIPI (Mantle Cell Lymphoma International Prognostic Index)","route":"/terms/mipi/"},{"id":"nsmp","kind":"term","name":"No specific molecular profile (NSMP) endometrial cancer","route":"/terms/nsmp/"},{"id":"pole-ultramutation","kind":"term","name":"POLE ultramutation (POLEmut)","route":"/terms/pole-ultramutation/"},{"id":"wild-type","kind":"term","name":"Wild-type (WT)","route":"/terms/wild-type/"},{"id":"wilms-risk-markers","kind":"term","name":"Wilms tumour risk markers (anaplasia, 1p/16q loss, 1q gain, SIOP and COG risk groups)","route":"/terms/wilms-risk-markers/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cll-treatment-naive","kind":"cancer","name":"Chronic lymphocytic leukaemia, first treatment","route":"/cancers/cll-treatment-naive/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"mds-higher-risk","kind":"cancer","name":"Higher-risk myelodysplastic syndromes","route":"/cancers/mds-higher-risk/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"plasma-cell-leukaemia","kind":"cancer","name":"Plasma cell leukaemia","route":"/cancers/plasma-cell-leukaemia/"},{"id":"richter-transformation-cll","kind":"cancer","name":"Richter transformation of chronic lymphocytic leukaemia","route":"/cancers/richter-transformation-cll/"},{"id":"aml-secondary","kind":"cancer","name":"Secondary and therapy-related acute myeloid leukaemia","route":"/cancers/aml-secondary/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"target":[{"id":"mdm2","kind":"target","name":"MDM2","route":"/targets/mdm2/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"paper":[{"id":"paper-hollstein-p53-mutations-science-1991","kind":"paper","name":"Hollstein 1991: p53 mutations in human cancers","route":"/key-papers/paper-hollstein-p53-mutations-science-1991/"},{"id":"paper-levine-p53-gatekeeper-cell-1997","kind":"paper","name":"Levine 1997: p53, the cellular gatekeeper for growth and division","route":"/key-papers/paper-levine-p53-gatekeeper-cell-1997/"},{"id":"paper-vogelstein-surfing-p53-network-nature-2000","kind":"paper","name":"Vogelstein, Lane and Levine 2000: surfing the p53 network","route":"/key-papers/paper-vogelstein-surfing-p53-network-nature-2000/"}],"biomarker":[{"id":"tp53-del17p","kind":"biomarker","name":"TP53 mutation and del(17p)","route":"/biomarkers/tp53-del17p/"}]}}