{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T09:21:25Z","timestamp":1771579285124,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: The tumor suppressor gene TP53 is one of the most frequently mutated genes in human cancers, with alterations predominantly affecting its DNA-binding domain (DBD). However, the mutational landscape and functional consequences of TP53 variants remain poorly characterized in African populations. This study aimed to characterize mutations in exons 5\u20136 of TP53 in oral cavity cancer (OCC), prostate cancer (PC), and breast cancer (BC) in a Senegalese population, and to assess their structural effects, functional consequences, and impact on protein\u2013protein interactions with BCL-2. Methods: Seventy-eight archived tumor DNA samples from Senegalese patients with OCC, PC, and BC were analyzed. Variants were annotated using COSMIC and dbSNP databases. Functional impact was evaluated with PolyPhen-2. Structural stability changes (\u0394\u0394G) were predicted using FoldX, conformational dynamics (\u0394\u0394Svib) were assessed with ENCoM, and effects on the p53\u2013BCL-2 interaction were analyzed using DDMut-PPI. Statistical analyses were also performed. Results: BC exhibited the highest TP53 mutation frequency, whereas OCC showed greater mutational diversity. Exon-level analysis revealed a significant enrichment of exon 6 mutations in BC. Structural analyses indicated that exon 5 mutations across all cancers and mutations in OCC were predominantly destabilizing and associated with loss-of-function effects. In contrast, recurrent exon 6 mutations in PC and BC, particularly V217L and V218M, were predicted to stabilize the p53 structure. Conformational dynamics differences between exons were significant only in PC. All analyzed mutations were predicted to stabilize the p53\u2013BCL-2 interaction. Conclusions: This integrative in silico study identified cancer and exon-specific TP53 mutation patterns in a Senegalese population, highlighting exon 6 as a context-dependent hotspot with potential oncogenic implication in PC and BC. Despite its computational nature, the study provides valuable insights that merit further investigation.<\/jats:p>","DOI":"10.3390\/genes17020245","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T08:50:03Z","timestamp":1771577403000},"page":"245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Computational Analysis of TP53 Exon 5\u20136 Mutations in Oral Cavity, Prostate, and Breast Cancers in a Senegalese Population"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9017-795X","authenticated-orcid":false,"given":"Mouhamed","family":"Mbaye","sequence":"first","affiliation":[{"name":"Pharmaceutical Biophysics Laboratory, Department of Pharmacy, Faculty of Medicine, Pharmacy and Odontology, Cheikh Anta Diop University, Dakar BP. 5005, Senegal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatimata","family":"Mbaye","sequence":"additional","affiliation":[{"name":"Genomics Laboratory, Department of Animal Biology, Faculty of Science and Technology, Cheikh Anta Diop University, Dakar BP. 5005, Senegal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mbacke","family":"Sembene","sequence":"additional","affiliation":[{"name":"Genomics Laboratory, Department of Animal Biology, Faculty of Science and Technology, Cheikh Anta Diop University, Dakar BP. 5005, Senegal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12943-024-02069-w","article-title":"Cancer, Metastasis, and the Epigenome","volume":"23","author":"Kiri","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a001008","DOI":"10.1101\/cshperspect.a001008","article-title":"TP53 Mutations in Human Cancers: Origins, Consequences, and Clinical Use","volume":"2","author":"Olivier","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_3","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":"ref_4","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/humu.22561","article-title":"Recommendations for Analyzing and Reporting TP53 Gene Variants in the High-Throughput Sequencing Era","volume":"35","author":"Soussi","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.1093\/nar\/gkh773","article-title":"Transcriptional Repression by P53 Promotes a Bcl-2-Insensitive and Mitochondria-Independent Pathway of Apoptosis","volume":"32","author":"Godefroy","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nrc883","article-title":"The Bcl2 Family: Regulators of the Cellular Life-or-Death Switch","volume":"2","author":"Cory","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/ijc.27767","article-title":"Distinct Tumor Protein P53 Mutants in Breast Cancer Subgroups","volume":"132","author":"Dumay","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/humu.20114","article-title":"Reassessment of theTP53 Mutation Database in Human Disease by Data Mining with a Library ofTP53 Missense Mutations","volume":"25","author":"Soussi","year":"2005","journal-title":"Hum. Mutat."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Huber, A.R., Van Hoeck, A., and Van Boxtel, R. (2021). The Mutagenic Impact of Environmental Exposures in Human Cells and Cancer: Imprints Through Time. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.760039"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41523-017-0007-9","article-title":"A Functionally Significant SNP in TP53 and Breast Cancer Risk in African-American Women","volume":"3","author":"Murphy","year":"2017","journal-title":"npj Breast Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41416-020-0831-9","article-title":"Trends in Cervical Cancer Incidence in Sub-Saharan Africa","volume":"123","author":"Joko","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"22","DOI":"10.14302\/issn.2572-3030.jcgb-22-4121","article-title":"Targeting Mutational Landscape of TP53 in Patients Diagnosed with Oral Cancer Living in Senegal","volume":"1","author":"Diaga","year":"2022","journal-title":"J. Cancer Genet. Biomark."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4236\/jct.2023.141003","article-title":"Bat 26 Microsatellite Instability in Oral Cavity Cancers in Senegal","volume":"14","author":"Samb","year":"2023","journal-title":"J. Cancer Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"71","DOI":"10.4236\/oju.2024.142008","article-title":"Prostate Cancer in the Thies Region, Senegal: Epidemiological, Diagnostic and Therapeutic Aspects","volume":"14","author":"Kouka","year":"2024","journal-title":"Open J. Urol."},{"key":"ref_15","first-page":"7","article-title":"Predicting Functional Effect of Human Missense Mutations Using PolyPhen-2","volume":"76","author":"Adzhubei","year":"2013","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4168","DOI":"10.1093\/bioinformatics\/btz184","article-title":"FoldX 5.0: Working with RNA, Small Molecules and a New Graphical Interface","volume":"35","author":"Delgado","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1093\/bioinformatics\/btac072","article-title":"pyFoldX: Enabling Biomolecular Analysis and Engineering along Structural Ensembles","volume":"38","author":"Radusky","year":"2022","journal-title":"Bioinformatics"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Capriotti, E., Fariselli, P., Rossi, I., and Casadio, R. (2008). A Three-State Prediction of Single Point Mutations on Protein Stability Changes. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-S2-S6"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"W350","DOI":"10.1093\/nar\/gky300","article-title":"DynaMut: Predicting the Impact of Mutations on Protein Conformation, Flexibility and Stability","volume":"46","author":"Rodrigues","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Frappier, V., and Najmanovich, R.J. (2014). A Coarse-Grained Elastic Network Atom Contact Model and Its Use in the Simulation of Protein Dynamics and the Prediction of the Effect of Mutations. PLoS Comput. Biol., 10.","DOI":"10.1371\/journal.pcbi.1003569"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"W207","DOI":"10.1093\/nar\/gkae412","article-title":"DDMut-PPI: Predicting Effects of Mutations on Protein\u2013Protein Interactions Using Graph-Based Deep Learning","volume":"52","author":"Zhou","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3742","DOI":"10.1210\/en.2016-1480","article-title":"A Convenient Method for Evaluating Epithelial Cell Proliferation in the Whole Mammary Glands of Female Mice","volume":"157","author":"Berryhill","year":"2016","journal-title":"Endocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s12558-012-0236-7","article-title":"Analyse de l\u2019\u00e9tat du stress oxydatif dans le cancer du sein \u00e0 l\u2019Ouest alg\u00e9rien via les tests FORD et FORT et corr\u00e9lation avec le grade histopronostique SBR","volume":"5","author":"Tahari","year":"2013","journal-title":"J. Afr. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"a030452","DOI":"10.1101\/cshperspect.a030452","article-title":"Androgen Signaling in Prostate Cancer","volume":"7","author":"Dai","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1177\/00220345221092751","article-title":"Areca Nut and Oral Cancer: Evidence from Studies Conducted in Humans","volume":"101","author":"Warnakulasuriya","year":"2022","journal-title":"J. Dent. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1002\/cncr.28150","article-title":"High Intratumor Genetic Heterogeneity Is Related to Worse Outcome in Patients with Head and Neck Squamous Cell Carcinoma","volume":"119","author":"Mroz","year":"2013","journal-title":"Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1002\/humu.22552","article-title":"TP53 Mutations in Human Cancer: Database Reassessment and Prospects for the Next Decade","volume":"35","author":"Leroy","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"200","DOI":"10.14715\/cmb\/2023.69.11.30","article-title":"Detection of TP53 Gene Mutation in Blood of Breast Cancer Patients Based on Circulating Tumor DNA and Its Application in Prognosis","volume":"69","author":"Lu","year":"2023","journal-title":"Cell. Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1007\/s00438-022-01914-1","article-title":"BRCA1, BRCA2, TP53, PIK3CA, PTEN and AKT1 Genes Mutations in Burkina Faso Breast Cancer Patients: Prevalence, Spectrum and Novel Variant","volume":"297","author":"Ouedraogo","year":"2022","journal-title":"Mol. Genet. Genom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1146\/annurev.biochem.77.060806.091238","article-title":"Structural Biology of the Tumor Suppressor P53","volume":"77","author":"Joerger","year":"2008","journal-title":"Annu. Rev. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s12288-024-01826-7","article-title":"Novel Mutations in Acute Erythroid Leukemia\u2013A Case Report with Review of Literature","volume":"41","author":"Jena","year":"2025","journal-title":"Indian J. Hematol. Blood Transfus."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1038\/s41467-025-57099-9","article-title":"Lipogenic Enzyme FASN Promotes Mutant P53 Accumulation and Gain-of-Function through Palmitoylation","volume":"16","author":"Liu","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrc2693","article-title":"When Mutants Gain New Powers: News from the Mutant P53 Field","volume":"9","author":"Brosh","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1101\/gad.190678.112","article-title":"Mutant P53: One Name, Many Proteins","volume":"26","author":"Prives","year":"2012","journal-title":"Genes Dev."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/2\/245\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T08:55:31Z","timestamp":1771577731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/2\/245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["genes17020245"],"URL":"https:\/\/doi.org\/10.3390\/genes17020245","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]}}}