{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:15:38Z","timestamp":1785842138323,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T00:00:00Z","timestamp":1594339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2013\/10\/E\/NZ5\/00663"],"award-info":[{"award-number":["2013\/10\/E\/NZ5\/00663"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vulvar squamous cell carcinoma (VSCC) originates from the progression of either a high-grade squamous intraepithelial lesion (HSIL) or differentiated-type vulvar intraepithelial neoplasia (dVIN), often in a background of lichen sclerosus (LS). The mechanisms leading to the progression of these premalignant lesions to VSCC are elusive. This study aims to identify pathogenic mutations implicated in VSCC development. Using next-generation sequencing, 38 HSIL, 19 dVIN, 20 LS, of which 10 were solitary lesions and 10 with adjacent VSCC, and 10 VSCC adjacent to LS, were screened for hotspot mutations in 50 genes covered by the Ion AmpliSeq Cancer Hotspot Panel v2 Kit (Thermo Fisher Scientific). Pathogenic mutations of TP53 were the most common genetic alterations identified in 53% and 24% of dVIN and HSIL cases, respectively, followed by CDKN2A (p16) mutated in 42% and 0% of dVIN and HSIL, respectively. Seven (70%) and three (30%) of 10 cases of VSCC associated with LS carried TP53 and CDKN2A mutations, respectively, whereas neither solitary LS nor LS associated with VSCC cases harbored mutations in these genes. It appears that TP53 mutations are early events during VSCC carcinogenesis, being present in both HSIL and dVIN lesions. Our preliminary data do not support a genetic background for the notion of LS as the VSCC premalignant lesion.<\/jats:p>","DOI":"10.3390\/ijms21144880","type":"journal-article","created":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T09:25:28Z","timestamp":1594373128000},"page":"4880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Somatic Mutation Profiling in Premalignant Lesions of Vulvar Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"21","author":[{"given":"Sebastian","family":"Zi\u0119ba","sequence":"first","affiliation":[{"name":"Department of Molecular Diagnostics, Holycross Cancer Centre, 25-734 Kielce, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Floor W.","family":"Pouwer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Radboud Institute for Health Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3718-999X","authenticated-orcid":false,"given":"Artur","family":"Kowalik","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics, Holycross Cancer Centre, 25-734 Kielce, Poland"},{"name":"Division of Medical Biology, Institute of Biology, Jan Kochanowski University, 25-406 Kielce, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil","family":"Zalewski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"},{"name":"Department of Gynecologic Oncology, Holycross Cancer Center, 25-734 Kielce, Poland"},{"name":"Chair and Department of Obstetrics, Gynecology and Oncology, 2nd Faculty of Medicine, Warsaw Medical University, 00-315 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Rusetska","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elwira","family":"Baku\u0142a-Zalewska","sequence":"additional","affiliation":[{"name":"Department of Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"Kopczy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Holycross Cancer Centre, 25-734 Kielce, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6138-1236","authenticated-orcid":false,"given":"Johanna M. A.","family":"Pijnenborg","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Radboud Institute for Health Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne A.","family":"de Hullu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Radboud Institute for Health Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3413-9612","authenticated-orcid":false,"given":"Magdalena","family":"Kowalewska","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"},{"name":"Department of Immunology, Biochemistry and Nutrition, Medical University of Warsaw, Centre for Preclinical Research and Technologies, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,10]]},"reference":[{"key":"ref_1","unstructured":"International Agency for Research on Cancer: Lyon, France, 2014."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.critrevonc.2008.02.012","article-title":"Review of squamous premalignant vulvar lesions","volume":"68","year":"2008","journal-title":"Crit Rev. 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