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This study analyzes genetic variants in key tumor suppressors and oncogenes across BOTS (with or without BRAF V600E), low-grade, and high-grade ovarian cancer using two next-generation sequencing gene panels, followed by Sanger confirmation and Western blot protein expression assessment.","Article  \nAn Analysis of Genetic Polymorphisms in 76 Genes Related to the Development of Ovarian Tumors of Different Aggressiveness  \nLaura A. Szafron 1, Piotr Sobiczewski 2, Agnieszka Dansonka-Mieszkowska 3, Jolanta Kupryjanczyk 4 and Lukasz M. Szafron 1, *  \nCitation: Szafron, L.A.; Sobiczewski, P.; Dansonka-Mieszkowska, A.; Kupryjanczyk, J.; Szafron, L.M. An Analysis of Genetic Polymorphisms in 76 Genes Related to the Development of Ovarian Tumors of Different Aggressiveness. Int. J. Mol. Sci. 2024, 25, 10876. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms252010876  \nAcademic Editor: Peter J. K. Kuppen  \nReceived: 30 July 2024  \nRevised: 12 September 2024  \nAccepted: 7 October 2024  \nPublished: 10 October 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; [laura.szafron@gmail.com](laura.szafron@gmail.com)  \n2 Department of Gynecological Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland  \n3 Cancer Molecular and Genetic Diagnostics Department, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland  \n4 Department of Cancer Pathomorphology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland  \n* Correspondence: [lukszafron@gmail.com](lukszafron@gmail.com)  \nAbstract: Borderline ovarian tumors (BOTS) are rare neoplasms of intermediate aggressiveness between cystadenomas and low-grade ovarian cancers (lgOvCa), which they share some molecular resemblances with. In contrast to the most frequent and well-described high-grade ovarian carcinomas (hgOvCa), the molecular background of BOTS and lgOvCa is less thoroughly characterized. Here, we aimed to analyze genetic variants in crucial tumor suppressors and oncogenes in BOTS (with or without the BRAF V600E mutation), lgOvCa, and hgOvCa in two gene panels using next-generation sequencing. Then, we verified the existence of selected polymorphisms by Sanger sequencing. Finally, Western blot analyses were carried out to check the impact of the selected polymorphisms on the expression of the corresponding proteins. Our study contributes to the molecular characterization of ovarian neoplasms, demonstrating divergent polymorphic patterns pointing to distinct signaling pathways engaged in their development. Certain mutations seem to play an important role in BOTS without the BRAF V600E variant (KRAS) and in lgOvCa (KRAS and NRAS), but not in hgOvCa. Additionally, based on multivariable regression analyses, potential biomarkers in BOTS (PARP1) and hgOvCa (FANCI, BRCA2, TSC2, FANCF) were identified. Noteworthy, for some of the analyzed genes, such as FANCI, FANCD2, and FANCI, FANCF, TSC2, the status of BRCA1/2 and TP53, respectively, turned out to be crucial. Our results shed new light on the similarities and differences in the polymorphic patterns between ovarian tumors of diverse aggressiveness. Furthermore, the biomarkers identified herein are of potential use as predictors of the prognosis and/or response to therapy.  \nKeywords: ovarian cancer; borderline ovarian tumor; DNA sequence variant; NGS; Western blot; TP53; RAS; BRAF; BRCA1/2  \n1. Introduction  \nOvarian carcinoma (OvCa) is a common and complex malignant disease with a generally poor outcome and an exceptionally high mortality worldwide [1] . There are two main types of OvCa: high-grade (hgOvCa) and low-grade (lgOvCa) ovarian carcinomas. The former is the most common type, characterized by extreme genomic instability, chromosomal rearrangements, and frequently mutated genes, especially tho","cbCaihdyUcQ3DZib","https://ap.wps.com/l/cbCaihdyUcQ3DZib","pdf",13692392,26,"English","en",105,"# Abstract\n# Keywords\n# Introduction","[{\"question\":\"What is the main research focus of the study?\",\"answer\":\"The study investigates genetic variants and polymorphisms in tumor-related genes across ovarian tumors with different aggressiveness levels, including BOTS, low-grade, and high-grade ovarian cancers.\"},{\"question\":\"How were genetic polymorphisms identified and validated?\",\"answer\":\"Genetic variants were analyzed using next-generation sequencing with two gene panels, then selected polymorphisms were verified by Sanger sequencing.\"},{\"question\":\"What experimental methods were used to assess functional impact?\",\"answer\":\"Western blot analyses were performed to examine how selected polymorphisms affect the expression of corresponding proteins.\"}]","An Analysis of Genetic Polymorphisms in 76 Genes Related to the Development of Ovarian Tumors of Different Aggressiveness | PDF",1789993372,66,{"code":4,"msg":82,"data":83},"ok",{"site_id":75,"language":74,"slug":84,"title":65,"keywords":85,"description":66,"schema_data":86,"social_meta":140,"head_meta":142,"extra_data":144,"updated_unix":145},"an-analysis-of-genetic-polymorphisms-in-76-genes-related-to-the-development-of-ovarian-tumors-of-different-aggressiveness","",{"@graph":87,"@context":139},[88,102,122],{"@type":89,"itemListElement":90},"BreadcrumbList",[91,95,97,100],{"item":92,"name":93,"@type":94,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":96,"name":9,"@type":94,"position":14},"https://docshare.wps.com/document/",{"item":98,"name":40,"@type":94,"position":99},"https://docshare.wps.com/document/research-report/",3,{"item":101,"name":65,"@type":94,"position":19},"https://docshare.wps.com/document/an-analysis-of-genetic-polymorphisms-in-76-genes-related-to-the-development-of-ovarian-tumors-of-different-aggressiveness/331468/",{"url":101,"name":65,"@type":103,"image":104,"author":109,"headline":65,"publisher":111,"fileFormat":114,"inLanguage":74,"description":66,"dateModified":115,"datePublished":116,"encodingFormat":114,"isAccessibleForFree":117,"interactionStatistic":118},"DigitalDocument",{"url":105,"@type":106,"width":107,"height":108},"https://docshare.wps.com/thumbnails/an-analysis-of-genetic-polymorphisms-in-76-genes-related-to-the-development-of-ovarian-tumors-of-different-aggressiveness/331468.png","ImageObject",300,407,{"name":63,"@type":110},"Person",{"url":92,"name":112,"@type":113},"DocShare","Organization","application/pdf","2026-11-04","2026-09-21",true,{"@type":119,"interactionType":120,"userInteractionCount":52},"InteractionCounter",{"@type":121},"ViewAction",{"@type":123,"mainEntity":124},"FAQPage",[125,131,135],{"name":126,"@type":127,"acceptedAnswer":128},"What is the main research focus of the study?","Question",{"text":129,"@type":130},"The study investigates genetic variants and polymorphisms in tumor-related genes across ovarian tumors with different aggressiveness levels, including BOTS, low-grade, and high-grade ovarian cancers.","Answer",{"name":132,"@type":127,"acceptedAnswer":133},"How were genetic polymorphisms identified and validated?",{"text":134,"@type":130},"Genetic variants were analyzed using next-generation sequencing with two gene panels, then selected polymorphisms were verified by Sanger sequencing.",{"name":136,"@type":127,"acceptedAnswer":137},"What experimental methods were used to assess functional impact?",{"text":138,"@type":130},"Western blot analyses were performed to examine how selected polymorphisms affect the expression of corresponding proteins.","https://schema.org",{"og:url":101,"og:type":141,"og:title":65,"og:site_name":112,"og:description":66},"article",{"robots":143,"canonical":101},"index,follow",{"doc_id":61,"site_id":75},1790198693]