{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:38:36Z","timestamp":1772138316418,"version":"3.50.1"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>An accurate assessment of p53\u2019s functional statuses is critical for cancer genomic medicine. However, there is a significant challenge in identifying tumors with non-mutational p53 inactivation which is not detectable through DNA sequencing. These undetected cases are often misclassified as p53-normal, leading to inaccurate prognosis and downstream association analyses. To address this issue, we built the support vector machine (SVM) models to systematically reassess p53\u2019s functional statuses in TP53 wild-type (TP53WT) tumors from multiple The Cancer Genome Atlas (TCGA) cohorts. Cross-validation demonstrated the good performance of the SVM models with a mean area under the receiver operating characteristic curve (AUROC) of 0.9822, precision of 0.9747, and recall of 0.9784. Our study revealed that a significant proportion (87%\u201399%) of TP53WT tumors actually had compromised p53 function. Additional analyses uncovered that these genetically intact but functionally impaired (termed as predictively reduced function of p53 or TP53WT-pRF) tumors exhibited genomic and pathophysiologic features akin to TP53-mutant tumors: heightened genomic instability and elevated levels of hypoxia. Clinically, patients with TP53WT-pRF tumors experienced significantly shortened overall survival or progression-free survival compared to those with predictively normal function of p53 (TP53WT-pN) tumors, and these patients also displayed increased sensitivity to platinum-based chemotherapy and radiation therapy.<\/jats:p>","DOI":"10.1093\/gpbjnl\/qzae064","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T13:59:39Z","timestamp":1727359179000},"source":"Crossref","is-referenced-by-count":1,"title":["Identify Non-mutational p53 Functional Deficiency in Human Cancers"],"prefix":"10.1093","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6984-5499","authenticated-orcid":false,"given":"Qianpeng","family":"Li","sequence":"first","affiliation":[{"name":"National Genomics Data Center, China National Center for Bioinformation , Beijing 100101,","place":["China"]},{"name":"Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4503-9907","authenticated-orcid":false,"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Genomics Data Center, China National Center for Bioinformation , Beijing 100101,","place":["China"]},{"name":"Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7729-6921","authenticated-orcid":false,"given":"Sicheng","family":"Luo","sequence":"additional","affiliation":[{"name":"National Genomics Data Center, China National Center for Bioinformation , Beijing 100101,","place":["China"]},{"name":"Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6603-5060","authenticated-orcid":false,"given":"Zhang","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Genomics Data Center, China National Center for Bioinformation , Beijing 100101,","place":["China"]},{"name":"Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2539-9807","authenticated-orcid":false,"given":"Ann L","family":"Oberg","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Mayo Clinic College of Medicine and Science , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8916-396X","authenticated-orcid":false,"given":"David E","family":"Kozono","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women\u2019s Hospital , Boston, MA 02215,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-7209","authenticated-orcid":false,"given":"Hua","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine , New Orleans, LA 70112,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7489-4885","authenticated-orcid":false,"given":"Jann N","family":"Sarkaria","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic College of Medicine and Science , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6390-6289","authenticated-orcid":false,"given":"Lina","family":"Ma","sequence":"additional","affiliation":[{"name":"National Genomics Data Center, China National Center for Bioinformation , Beijing 100101,","place":["China"]},{"name":"Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2072-4826","authenticated-orcid":false,"given":"Liguo","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Mayo Clinic College of Medicine and Science , Rochester, MN 55905,","place":["USA"]},{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science , Rochester, MN 55905","place":[", USA"]},{"name":"Bioinformatics and Computational Biology Graduate Program, University of Minnesota Rochester , Rochester, MN 55904,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"2025010621065609200_qzae064-B1","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1126\/science.1235122","article-title":"Cancer genome landscapes","volume":"339","author":"Vogelstein","year":"2013","journal-title":"Science"},{"key":"2025010621065609200_qzae064-B2","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/nature08645","article-title":"Complex landscapes of somatic rearrangement in human breast cancer genomes","volume":"462","author":"Stephens","year":"2009","journal-title":"Nature"},{"key":"2025010621065609200_qzae064-B3","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"2025010621065609200_qzae064-B4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nrm2147","article-title":"p53 in health and disease","volume":"8","author":"Vousden","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025010621065609200_qzae064-B5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41418-018-0246-9","article-title":"Mutant p53 as a guardian of the cancer cell","volume":"26","author":"Mantovani","year":"2019","journal-title":"Cell Death Differ"},{"key":"2025010621065609200_qzae064-B6","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/s41418-022-00943-y","article-title":"p53 in ferroptosis regulation: the new weapon for the old guardian","volume":"29","author":"Liu","year":"2022","journal-title":"Cell Death Differ"},{"key":"2025010621065609200_qzae064-B7","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.celrep.2018.12.066","article-title":"Characterization of tumor-suppressor gene inactivation events in 33 cancer types","volume":"26","author":"Jia","year":"2019","journal-title":"Cell Rep"},{"key":"2025010621065609200_qzae064-B8","doi-asserted-by":"crossref","first-page":"3943","DOI":"10.1038\/onc.2016.502","article-title":"Census and evaluation of p53 target genes","volume":"36","author":"Fischer","year":"2017","journal-title":"Oncogene"},{"key":"2025010621065609200_qzae064-B9","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/978-94-017-9211-0_8","article-title":"Mutant p53 and the response to chemotherapy and radiation","volume":"85","author":"Tchelebi","year":"2014","journal-title":"Subcell Biochem"},{"key":"2025010621065609200_qzae064-B10","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1158\/1078-0432.CCR-11-2260","article-title":"TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation-induced senescence","volume":"18","author":"Skinner","year":"2012","journal-title":"Clin Cancer Res"},{"key":"2025010621065609200_qzae064-B11","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1126\/science.7973635","article-title":"p53 status and the efficacy of cancer therapy in vivo","volume":"266","author":"Lowe","year":"1994","journal-title":"Science"},{"key":"2025010621065609200_qzae064-B12","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1371\/journal.pmed.0040090","article-title":"Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen","volume":"4","author":"Bertheau","year":"2007","journal-title":"PLoS Med"},{"key":"2025010621065609200_qzae064-B13","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/S0140-6736(02)09969-5","article-title":"Effect of mutated TP53 on response of advanced breast cancers to high-dose chemotherapy","volume":"360","author":"Bertheau","year":"2002","journal-title":"Lancet"},{"key":"2025010621065609200_qzae064-B14","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0304-3835(99)00393-6","article-title":"p53-dependent radioresistance in ovarian carcinoma cell lines","volume":"150","author":"Concin","year":"2000","journal-title":"Cancer Lett"},{"key":"2025010621065609200_qzae064-B15","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1158\/0008-5472.CAN-16-2832","article-title":"Local activation of p53 in the tumor microenvironment overcomes immune suppression and enhances antitumor immunity","volume":"77","author":"Guo","year":"2017","journal-title":"Cancer Res"},{"key":"2025010621065609200_qzae064-B16","doi-asserted-by":"crossref","first-page":"djv303","DOI":"10.1093\/jnci\/djv303","article-title":"PDL1 regulation by p53 via miR-34","volume":"108","author":"Cortez","year":"2016","journal-title":"J Natl Cancer Inst"},{"key":"2025010621065609200_qzae064-B17","doi-asserted-by":"crossref","first-page":"e2025631118","DOI":"10.1073\/pnas.2025631118","article-title":"TP53 missense mutations in PDAC are associated with enhanced fibrosis and an immunosuppressive microenvironment","volume":"118","author":"Maddalena","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025010621065609200_qzae064-B18","doi-asserted-by":"crossref","first-page":"7262","DOI":"10.1073\/pnas.89.15.7262","article-title":"Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion","volume":"89","author":"Moll","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025010621065609200_qzae064-B19","first-page":"790","article-title":"p53 gene mutations, p53 protein accumulation and compartmentalization in colorectal adenocarcinoma","volume":"147","author":"Bosari","year":"1995","journal-title":"Am J Pathol"},{"key":"2025010621065609200_qzae064-B20","doi-asserted-by":"crossref","first-page":"4407","DOI":"10.1073\/pnas.92.10.4407","article-title":"Wild-type p53 protein undergoes cytoplasmic sequestration in undifferentiated neuroblastomas but not in differentiated tumors","volume":"92","author":"Moll","year":"1995","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025010621065609200_qzae064-B21","first-page":"2653","article-title":"Frequently elevated content of immunochemically defined wild-type p53 protein in colorectal adenomas","volume":"8","author":"Tominaga","year":"1993","journal-title":"Oncogene"},{"key":"2025010621065609200_qzae064-B22","first-page":"545","article-title":"Differential subcellular p53 localization and function in N- and S-type neuroblastoma cell lines","volume":"9","author":"Isaacs","year":"1998","journal-title":"Cell Growth Differ"},{"key":"2025010621065609200_qzae064-B23","doi-asserted-by":"crossref","first-page":"e06498","DOI":"10.7554\/eLife.06498","article-title":"A distinct p53 target gene set predicts for response to the selective p53\u2013HDM2 inhibitor NVP-CGM097","volume":"4","author":"Jeay","year":"2015","journal-title":"Elife"},{"key":"2025010621065609200_qzae064-B24","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.1158\/0008-5472.CAN-17-0949","article-title":"Predictive gene signatures determine tumor sensitivity to MDM2 inhibition","volume":"78","author":"Ishizawa","year":"2018","journal-title":"Cancer Res"},{"key":"2025010621065609200_qzae064-B25","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/sj.cdd.4401182","article-title":"Regulation of p53 responses by post-translational modifications","volume":"10","author":"Xu","year":"2003","journal-title":"Cell Death Differ"},{"key":"2025010621065609200_qzae064-B26","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nature03117","article-title":"Regulation of p53 activity through lysine methylation","volume":"432","author":"Chuikov","year":"2004","journal-title":"Nature"},{"key":"2025010621065609200_qzae064-B27","doi-asserted-by":"crossref","first-page":"745","DOI":"10.3390\/cancers13040745","article-title":"Regulation of p53 by E3s","volume":"13","author":"Pan","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2025010621065609200_qzae064-B28","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1038\/emboj.2009.164","article-title":"Differential regulation of p53 and p21 by MKRN1 E3 ligase controls cell cycle arrest and apoptosis","volume":"28","author":"Lee","year":"2009","journal-title":"EMBO J"},{"key":"2025010621065609200_qzae064-B29","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.1074\/jbc.M805658200","article-title":"MSL2 promotes Mdm2-independent cytoplasmic localization of p53","volume":"284","author":"Kruse","year":"2009","journal-title":"J Biol Chem"},{"key":"2025010621065609200_qzae064-B30","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s00401-005-1041-5","article-title":"TP53 promoter methylation in human gliomas","volume":"110","author":"Amatya","year":"2005","journal-title":"Acta Neuropathol"},{"key":"2025010621065609200_qzae064-B31","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41580-019-0110-x","article-title":"The multiple mechanisms that regulate p53 activity and cell fate","volume":"20","author":"Hafner","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025010621065609200_qzae064-B32","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.3390\/ijms17122029","article-title":"TP53\/microRNA interplay in hepatocellular carcinoma","volume":"17","author":"Pollutri","year":"2016","journal-title":"Int J Mol Sci"},{"key":"2025010621065609200_qzae064-B33","doi-asserted-by":"crossref","first-page":"5316","DOI":"10.1073\/pnas.1202465109","article-title":"microRNAs\/TP53 feedback circuitry in glioblastoma multiforme","volume":"109","author":"Suh","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025010621065609200_qzae064-B34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"Hanzelmann","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2025010621065609200_qzae064-B35","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature08460","article-title":"Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1","volume":"462","author":"Barbie","year":"2009","journal-title":"Nature"},{"key":"2025010621065609200_qzae064-B36","doi-asserted-by":"crossref","first-page":"e1000217","DOI":"10.1371\/journal.pcbi.1000217","article-title":"Inferring pathway activity toward precise disease classification","volume":"4","author":"Lee","year":"2008","journal-title":"PLoS Comput Biol"},{"key":"2025010621065609200_qzae064-B37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/1471-2105-6-225","article-title":"Pathway level analysis of gene expression using singular value decomposition","volume":"6","author":"Tomfohr","year":"2005","journal-title":"BMC Bioinformatics"},{"key":"2025010621065609200_qzae064-B38","first-page":"D180","article-title":"ReMap 2020: a database of regulatory regions from an integrative analysis of human and Arabidopsis DNA-binding sequencing experiments","volume":"48","author":"Cheneby","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2025010621065609200_qzae064-B39","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/nsmb.3452","article-title":"p53 pulses lead to distinct patterns of gene expression albeit similar DNA-binding dynamics","volume":"24","author":"Hafner","year":"2017","journal-title":"Nat Struct Mol Biol"},{"key":"2025010621065609200_qzae064-B40","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/sj.onc.1203366","article-title":"Tissue and cell-specific expression of the p53-target genes: bax, fas, mdm2 and waf1\/p21, before and following ionising irradiation in mice","volume":"19","author":"Bouvard","year":"2000","journal-title":"Oncogene"},{"key":"2025010621065609200_qzae064-B41","doi-asserted-by":"crossref","first-page":"4601","DOI":"10.1038\/sj.onc.1204484","article-title":"Tissue specific expression of p53 target genes suggests a key role for KILLER\/DR5 in p53-dependent apoptosis in vivo","volume":"20","author":"Burns","year":"2001","journal-title":"Oncogene"},{"key":"2025010621065609200_qzae064-B42","doi-asserted-by":"crossref","first-page":"10720","DOI":"10.1074\/jbc.RA119.007965","article-title":"Control of p53-dependent transcription and enhancer activity by the p53 family member p63","volume":"294","author":"Karsli Uzunbas","year":"2019","journal-title":"J Biol Chem"},{"key":"2025010621065609200_qzae064-B43","doi-asserted-by":"crossref","first-page":"8424","DOI":"10.1073\/pnas.1431692100","article-title":"Understanding the function-structure and function\u2013mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis","volume":"100","author":"Kato","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025010621065609200_qzae064-B44","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1200\/JCO.2008.18.1370","article-title":"Supervised risk predictor of breast cancer based on intrinsic subtypes","volume":"27","author":"Parker","year":"2009","journal-title":"J Clin Oncol"},{"key":"2025010621065609200_qzae064-B45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/358015a0","article-title":"p53, guardian of the genome","volume":"358","author":"Lane","year":"1992","journal-title":"Nature"},{"key":"2025010621065609200_qzae064-B46","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0092-8674(00)81871-1","article-title":"p53, the cellular gatekeeper for growth and division","volume":"88","author":"Levine","year":"1997","journal-title":"Cell"},{"key":"2025010621065609200_qzae064-B47","doi-asserted-by":"crossref","first-page":"6334","DOI":"10.1073\/pnas.0911082107","article-title":"p53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis","volume":"107","author":"Yamakuchi","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025010621065609200_qzae064-B48","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1101\/gad.14.1.34","article-title":"Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha","volume":"14","author":"Ravi","year":"2000","journal-title":"Genes Dev"},{"key":"2025010621065609200_qzae064-B49","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1038\/cddis.2011.48","article-title":"Reciprocal influence of the p53 and the hypoxic pathways","volume":"2","author":"Sermeus","year":"2011","journal-title":"Cell Death Dis"},{"key":"2025010621065609200_qzae064-B50","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/sj.bjc.6605450","article-title":"Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene","volume":"102","author":"Buffa","year":"2010","journal-title":"Br J Cancer"},{"key":"2025010621065609200_qzae064-B51","doi-asserted-by":"crossref","first-page":"5742","DOI":"10.1073\/pnas.90.12.5742","article-title":"p53 mutations increase resistance to ionizing radiation","volume":"90","author":"Lee","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025010621065609200_qzae064-B52","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1038\/s41388-020-1250-3","article-title":"Radiation resistance in head and neck squamous cell carcinoma: dire need for an appropriate sensitizer","volume":"39","author":"Hutchinson","year":"2020","journal-title":"Oncogene"},{"key":"2025010621065609200_qzae064-B53","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/ijc.32598","article-title":"Radioresistance of KRAS\/TP53-mutated lung cancer can be overcome by radiation dose escalation or EGFR tyrosine kinase inhibition in vivo","volume":"147","author":"Gurtner","year":"2020","journal-title":"Int J Cancer"},{"key":"2025010621065609200_qzae064-B54","doi-asserted-by":"crossref","first-page":"229ra42","DOI":"10.1126\/scitranslmed.3008291","article-title":"DNA repair pathway gene expression score correlates with repair proficiency and tumor sensitivity to chemotherapy","volume":"6","author":"Pitroda","year":"2014","journal-title":"Sci Transl Med"},{"key":"2025010621065609200_qzae064-B55","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.1158\/1078-0432.CCR-14-2898","article-title":"Development and validation of a novel radiosensitivity signature in human breast cancer","volume":"21","author":"Speers","year":"2015","journal-title":"Clin Cancer Res"},{"key":"2025010621065609200_qzae064-B56","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1158\/1078-0432.CCR-19-0909","article-title":"Genomic and phenotypic characterization of a broad panel of patient-derived xenografts reflects the diversity of glioblastoma","volume":"26","author":"Vaubel","year":"2020","journal-title":"Clin Cancer Res"},{"key":"2025010621065609200_qzae064-B57","doi-asserted-by":"crossref","first-page":"e2200085","DOI":"10.1200\/PO.22.00085","article-title":"Utility of homologous recombination deficiency biomarkers across cancer types","volume":"6","author":"Takamatsu","year":"2022","journal-title":"JCO Precis Oncol"},{"key":"2025010621065609200_qzae064-B58","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/sj.cdd.4401903","article-title":"p53 in recombination and repair","volume":"13","author":"Gatz","year":"2006","journal-title":"Cell Death Differ"},{"key":"2025010621065609200_qzae064-B59","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nrm1546","article-title":"p53: traffic cop at the crossroads of DNA repair and recombination","volume":"6","author":"Sengupta","year":"2005","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025010621065609200_qzae064-B60","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1016\/j.celrep.2019.07.001","article-title":"Integrated analysis of TP53 gene and pathway alterations in The Cancer Genome Atlas","volume":"28","author":"Donehower","year":"2019","journal-title":"Cell Rep"},{"key":"2025010621065609200_qzae064-B61","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1146\/annurev-biochem-060815-014710","article-title":"The p53 pathway: origins, inactivation in cancer, and emerging therapeutic approaches","volume":"85","author":"Joerger","year":"2016","journal-title":"Annu Rev Biochem"},{"key":"2025010621065609200_qzae064-B62","doi-asserted-by":"crossref","first-page":"a026211","DOI":"10.1101\/cshperspect.a026211","article-title":"Attenuating the p53 pathway in human cancers: many means to the same end","volume":"6","author":"Wasylishen","year":"2016","journal-title":"Cold Spring Harb Perspect Med"},{"key":"2025010621065609200_qzae064-B63","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/387296a0","article-title":"Mdm2 promotes the rapid degradation of p53","volume":"387","author":"Haupt","year":"1997","journal-title":"Nature"},{"key":"2025010621065609200_qzae064-B64","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1101\/gad.304071.117","article-title":"Wild-type and cancer-related p53 proteins are preferentially degraded by MDM2 as dimers rather than tetramers","volume":"32","author":"Katz","year":"2018","journal-title":"Genes Dev"},{"key":"2025010621065609200_qzae064-B65","doi-asserted-by":"crossref","first-page":"4419","DOI":"10.1158\/1078-0432.CCR-14-0899","article-title":"TP53 mutations and lung cancer: not all mutations are created equal","volume":"20","author":"Govindan","year":"2014","journal-title":"Clin Cancer Res"},{"key":"2025010621065609200_qzae064-B66","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1101\/gad.190678.112","article-title":"Mutant p53: one name, many proteins","volume":"26","author":"Freed-Pastor","year":"2012","journal-title":"Genes Dev"},{"key":"2025010621065609200_qzae064-B67","doi-asserted-by":"crossref","first-page":"a001107","DOI":"10.1101\/cshperspect.a001107","article-title":"Mutant p53 gain-of-function in cancer","volume":"2","author":"Oren","year":"2010","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2025010621065609200_qzae064-B68","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1126\/science.1905840","article-title":"p53 mutations in human cancers","volume":"253","author":"Hollstein","year":"1991","journal-title":"Science"},{"key":"2025010621065609200_qzae064-B69","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nrc3711","article-title":"Unravelling mechanisms of p53-mediated tumour suppression","volume":"14","author":"Bieging","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"2025010621065609200_qzae064-B70","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.ccr.2006.09.013","article-title":"Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis","volume":"10","author":"Derksen","year":"2006","journal-title":"Cancer Cell"},{"key":"2025010621065609200_qzae064-B71","doi-asserted-by":"crossref","first-page":"162","DOI":"10.3390\/cancers10060162","article-title":"p53-dependent and -independent epithelial integrity: beyond miRNAs and metabolic fluctuations","volume":"10","author":"Oikawa","year":"2018","journal-title":"Cancers (Basel)"},{"key":"2025010621065609200_qzae064-B72","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1038\/s41467-021-21997-5","article-title":"Deep generative neural network for accurate drug response imputation","volume":"12","author":"Jia","year":"2021","journal-title":"Nat Commun"},{"key":"2025010621065609200_qzae064-B73","doi-asserted-by":"crossref","first-page":"8971","DOI":"10.1038\/ncomms9971","article-title":"Systematic pan-cancer analysis of tumour purity","volume":"6","author":"Aran","year":"2015","journal-title":"Nat Commun"},{"key":"2025010621065609200_qzae064-B74","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1126\/science.1262110","article-title":"The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans","volume":"348","author":"GTEx Consortium","year":"2015","journal-title":"Science"},{"key":"2025010621065609200_qzae064-B75","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2025010621065609200_qzae064-B76","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/s41588-019-0569-6","article-title":"Genomic landscape of lung adenocarcinoma in East Asians","volume":"52","author":"Chen","year":"2020","journal-title":"Nat Genet"},{"key":"2025010621065609200_qzae064-B77","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"}],"container-title":["Genomics, Proteomics &amp; Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/gpb\/advance-article-pdf\/doi\/10.1093\/gpbjnl\/qzae064\/59357691\/qzae064.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/gpb\/article-pdf\/22\/5\/qzae064\/59357691\/qzae064.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/gpb\/article-pdf\/22\/5\/qzae064\/59357691\/qzae064.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T16:09:50Z","timestamp":1736179790000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/gpb\/article\/doi\/10.1093\/gpbjnl\/qzae064\/7777166"}},"subtitle":[],"editor":[{"given":"Leng","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,9,26]]},"references-count":77,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,12,3]]}},"URL":"https:\/\/doi.org\/10.1093\/gpbjnl\/qzae064","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.07.28.501874","asserted-by":"object"}]},"ISSN":["1672-0229","2210-3244"],"issn-type":[{"value":"1672-0229","type":"print"},{"value":"2210-3244","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,10]]},"published":{"date-parts":[[2024,9,26]]},"article-number":"qzae064"}}