{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:44:29Z","timestamp":1753875869406,"version":"3.41.2"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Macau Science and Technology Development Fund","award":["085\/2017\/A2","0077\/2019\/AMJ","0032-2022-A1"],"award-info":[{"award-number":["085\/2017\/A2","0077\/2019\/AMJ","0032-2022-A1"]}]},{"DOI":"10.13039\/501100004733","name":"University of Macau","doi-asserted-by":"publisher","award":["SRG2017-00097-FHS","MYRG2019-00018-FHS","2020-00094-FHS"],"award-info":[{"award-number":["SRG2017-00097-FHS","MYRG2019-00018-FHS","2020-00094-FHS"]}],"id":[{"id":"10.13039\/501100004733","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Faculty of Health Sciences of University of Macau","award":["FHSIG\/SW\/0007\/2020P"],"award-info":[{"award-number":["FHSIG\/SW\/0007\/2020P"]}]},{"name":"Macau Science and Technology Development Fund","award":["0155\/2023\/RIA3","0048\/2022\/A"],"award-info":[{"award-number":["0155\/2023\/RIA3","0048\/2022\/A"]}]},{"DOI":"10.13039\/501100004733","name":"University of Macau","doi-asserted-by":"publisher","award":["MYRG2022-00023-FHS"],"award-info":[{"award-number":["MYRG2022-00023-FHS"]}],"id":[{"id":"10.13039\/501100004733","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Faculty of Health Sciences of University of Macau","award":["SRG2024-00014-FHS"],"award-info":[{"award-number":["SRG2024-00014-FHS"]}]},{"name":"University of Macau Postdoctoral Fellowship Class A of the Macao Talent Program and Postdoctoral Fellowship of Macau Science and Technology Development Fund","award":["UMMTP-FDCT\/0027\/APD\/2021"],"award-info":[{"award-number":["UMMTP-FDCT\/0027\/APD\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Somatic variation is a major type of genetic variation contributing to human diseases including cancer. Of the vast quantities of somatic variants identified, the functional impact of many somatic variants, in particular the missense variants, remains unclear. Lack of the functional information prevents the translation of rich variation data into clinical applications. We previously developed a method named Ramachandran Plot\u2013Molecular Dynamics Simulations (RP-MDS), aiming to predict the function of germline missense variants based on their effects on protein structure stability, and successfully applied to predict the deleteriousness of unclassified germline missense variants in multiple cancer genes. We hypothesized that regardless of their different genetic origins, somatic missense variants and germline missense variants could have similar effects on the stability of their affected protein structure. As such, the RP-MDS method designed for germline missense variants should also be applicable to predict the function of somatic missense variants. In the current study, we tested our hypothesis by using the somatic missense variants in TP53 as a model. Of the 397 somatic missense variants analyzed, RP-MDS predicted that 195 (49.1%) variants were deleterious as they significantly disturbed p53 structure. The results were largely validated by using a p53\u2013p21 promoter\u2013green fluorescent protein (GFP) reporter gene assay. Our study demonstrated that deleterious somatic missense variants can be identified by referring to their effects on protein structural stability.<\/jats:p>","DOI":"10.1093\/bib\/bbae400","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T12:39:33Z","timestamp":1723639173000},"source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive classification of <i>TP53<\/i> somatic missense variants based on their impact on p53 structural stability"],"prefix":"10.1093","volume":"25","author":[{"given":"Benjamin","family":"Tam","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, University Avenue , Taipa, Macau SAR 999078 , China"}]},{"given":"Philip Naderev P","family":"Lagniton","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, University Avenue , Taipa, Macau SAR 999078 , China"}]},{"given":"Mariano","family":"Da Luz","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, University Avenue , Taipa, Macau SAR 999078 , China"}]},{"given":"Bojin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, University Avenue , Taipa, Macau SAR 999078 , China"}]},{"given":"Siddharth","family":"Sinha","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, University Avenue , Taipa, Macau SAR 999078 , China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0904-554X","authenticated-orcid":false,"given":"Chon Lok","family":"Lei","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, University Avenue , Taipa, Macau SAR 999078 , China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-1320","authenticated-orcid":false,"given":"San Ming","family":"Wang","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, University Avenue , Taipa, Macau SAR 999078 , China"}]}],"member":"286","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"key":"2024081412391243700_ref1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev-pathol-011110-130206","article-title":"EGFR mutations and lung cancer","volume":"6","author":"Cunha","year":"2011","journal-title":"Annu Rev Pathol"},{"key":"2024081412391243700_ref2","doi-asserted-by":"crossref","first-page":"viii83","DOI":"10.1093\/annonc\/mdt313","article-title":"Hereditary ovarian and breast cancer: what have we learned?","volume":"24","author":"Lynch","year":"2013","journal-title":"Ann Oncol"},{"key":"2024081412391243700_ref3","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular 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