dc.contributor.author | Holý, Petr | |
dc.contributor.author | Hlaváč, Viktor | |
dc.contributor.author | Šeborová, Karolína | |
dc.contributor.author | Šůsová, Simona | |
dc.contributor.author | Tesařová, Tereza | |
dc.contributor.author | Rob, Lukáš | |
dc.contributor.author | Hruda, Martin | |
dc.contributor.author | Bouda, Jiří | |
dc.contributor.author | Bartáková, Alena | |
dc.contributor.author | Mrhalová, Marcela | |
dc.contributor.author | Kopečková, Kateřina | |
dc.contributor.author | Al Obeed Allah, Mohammad Moufaq Khatar | |
dc.contributor.author | Špaček, Jiří | |
dc.contributor.author | Sedláková, Iva | |
dc.contributor.author | Souček, Pavel | |
dc.contributor.author | Václavíková, Radka | |
dc.date.accessioned | 2024-03-18T08:10:39Z | |
dc.date.available | 2024-03-18T08:10:39Z | |
dc.date.issued | 2024 | |
dc.identifier.uri | https://hdl.handle.net/20.500.14178/2401 | |
dc.description.abstract | High-grade serous ovarian carcinoma (HGSC) is the most common subtype of ovarian cancer and is among the most fatal gynecological malignancies worldwide, due to late diagnosis at advanced stages and frequent therapy resistance. In 47 HGSC patients, we assessed somatic and germline genetic variability of a custom panel of 144 known or suspected HGSC-related genes by high-coverage targeted DNA sequencing to identify the genetic determinants associated with resistance to platinum-based therapy. In the germline, the most mutated genes were DNAH14 (17%), RAD51B (17%), CFTR (13%), BRCA1 (11%), and RAD51 (11%). Somatically, the most mutated gene was TP53 (98%), followed by CSMD1/2/3 (19/19/36%), and CFTR (23%). Results were compared with those from whole exome sequencing of a similar set of 35 HGSC patients. Somatic variants in TP53 were also validated using GENIE data of 1287 HGSC samples. Our approach showed increased prevalence of high impact somatic and germline mutations, especially those affecting splice sites of TP53, compared to validation datasets. Furthermore, nonsense TP53 somatic mutations were negatively associated with patient survival. Elevated TP53 transcript levels were associated with platinum resistance and presence of TP53 missense mutations, while decreased TP53 levels were found in tumors carrying mutations with predicted high impact, which was confirmed in The Cancer Genome Atlas data (n = 260). Targeted DNA sequencing of TP53 combined with transcript quantification may contribute to the concept of precision oncology of HGSC. Future studies should explore targeting the p53 pathway based on specific mutation types and co-analyze the expression and mutational profiles of other key cancer genes. | en |
dc.language.iso | en | |
dc.relation.url | https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34908 | |
dc.rights | Creative Commons Uveďte původ 4.0 International | cs |
dc.rights | Creative Commons Attribution 4.0 International | en |
dc.title | Targeted DNA sequencing of high-grade serous ovarian carcinoma reveals association of TP53 mutations with platinum resistance when combined with gene expression | en |
dcterms.accessRights | openAccess | |
dcterms.license | https://creativecommons.org/licenses/by/4.0/legalcode | |
dc.date.updated | 2025-01-15T10:11:02Z | |
dc.subject.keyword | biomarkers | en |
dc.subject.keyword | ovarian carcinoma | en |
dc.subject.keyword | platinum resistance | en |
dc.subject.keyword | TP53 | en |
dc.subject.keyword | treatment response | en |
dc.identifier.eissn | 1097-0215 | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/MZ0/NU/NU20-09-00174 | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/UK/I-UK/I-LFP | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/FN/I-FN/I-FNM | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/UK/COOP/COOP | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/MZ0/NU/NU20-09-00174 | |
dc.date.embargoStartDate | 2025-01-15 | |
dc.type.obd | 73 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | |
dc.identifier.doi | 10.1002/ijc.34908 | |
dc.identifier.utWos | 001180449400001 | |
dc.identifier.eidScopus | 2-s2.0-85187176229 | |
dc.identifier.obd | 645959 | |
dc.identifier.pubmed | 38447012 | |
dc.subject.rivPrimary | 30000::30200::30204 | |
dcterms.isPartOf.name | International Journal of Cancer | |
dcterms.isPartOf.issn | 0020-7136 | |
dcterms.isPartOf.journalYear | 2024 | |
dcterms.isPartOf.journalVolume | 155 | |
dcterms.isPartOf.journalIssue | 1 | |
uk.faculty.primaryId | 111 | |
uk.faculty.primaryName | Lékařská fakulta v Plzni | cs |
uk.faculty.primaryName | Faculty of Medicine in Pilsen | en |
uk.faculty.secondaryId | 109 | |
uk.faculty.secondaryId | 54 | |
uk.faculty.secondaryId | 51 | |
uk.faculty.secondaryId | 110 | |
uk.faculty.secondaryId | 52 | |
uk.faculty.secondaryName | 2. lékařská fakulta | cs |
uk.faculty.secondaryName | Second Faculty of Medicine | en |
uk.faculty.secondaryName | Fakultní nemocnice Plzeň | cs |
uk.faculty.secondaryName | University Hospital in Pilsen | en |
uk.faculty.secondaryName | Fakultní nemocnice Hradec Králové | cs |
uk.faculty.secondaryName | University Hospital Hradec Králové | en |
uk.faculty.secondaryName | 3. lékařská fakulta | cs |
uk.faculty.secondaryName | Third Faculty of Medicine | en |
uk.faculty.secondaryName | Fakultní nemocnice v Motole | cs |
uk.faculty.secondaryName | Motol University Hospital | en |
uk.department.primaryId | 100012968318 | |
uk.department.primaryName | Biomedicínské centrum | cs |
uk.department.primaryName | Biomedical Center | en |
uk.department.secondaryId | 5000002699 | |
uk.department.secondaryId | 100010693437 | |
uk.department.secondaryId | 1705 | |
uk.department.secondaryId | 1398 | |
uk.department.secondaryId | 2350 | |
uk.department.secondaryId | 5000000027 | |
uk.department.secondaryId | 619 | |
uk.department.secondaryName | Gynekologicko-porodnická klinika | cs |
uk.department.secondaryName | Department of Obstetrics and Gynecology | en |
uk.department.secondaryName | Onkologická klinika 2. LF UK a FN Motol | cs |
uk.department.secondaryName | Deaprtment of Oncology, 2nd Faculty of Medicine and Motol University Hospital | en |
uk.department.secondaryName | Ústav patologie a molekulární medicíny | cs |
uk.department.secondaryName | Ústav patologie a molekulární medicíny | en |
uk.department.secondaryName | Gynekologicko-porodnická klinika | cs |
uk.department.secondaryName | Department of Gynaecology and Obstetrics | en |
uk.department.secondaryName | Onkologická klinika | cs |
uk.department.secondaryName | Department of Oncology | en |
uk.department.secondaryName | Porodnická a gynekologická klinika | cs |
uk.department.secondaryName | Department of Obstetrics and Gynecology | en |
uk.department.secondaryName | Gynekologicko-porodnická klinika 3. LF UK a FNKV | cs |
uk.department.secondaryName | Department of Gynecology and Obstetrics 3FM CU and UHKV | en |
dc.description.pageRange | 104-116 | |
dc.type.obdHierarchyCs | ČLÁNEK V ČASOPISU::článek v časopisu::původní článek | cs |
dc.type.obdHierarchyEn | JOURNAL ARTICLE::journal article::original article | en |
dc.type.obdHierarchyCode | 73::152::206 | en |
uk.displayTitle | Targeted DNA sequencing of high-grade serous ovarian carcinoma reveals association of TP53 mutations with platinum resistance when combined with gene expression | en |