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OSCC patients with lymph node metastases at diagnosis underwent primary surgery, with multiple spatially distinct samples sequenced using an Illumina cancer panel. Results reveal extensive inter- and intratumor heterogeneity, with TP53 as the most frequently mutated gene and supporting evidence for field cancerization and clonal selection through differing tumor mutational burden between primary tumors and metastases.",{"@graph":69,"@context":127},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/genomic-alterations-in-the-stepwise-progression-from-normal-mucosa-to-metastasizing-oral-squamous-cell-carcinoma/328990/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/genomic-alterations-in-the-stepwise-progression-from-normal-mucosa-to-metastasizing-oral-squamous-cell-carcinoma/328990.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119,123],{"name":110,"@type":111,"acceptedAnswer":112},"What was the aim of the study on OSCC progression?","Question",{"text":113,"@type":114},"To investigate genomic changes occurring from dysplasia and morphologically normal mucosa to invasive OSCC and regional lymph node metastases.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were patient samples collected and analyzed?",{"text":118,"@type":114},"Multiple tissue regions around the cancer, from cancer tissue, and within lymph node metastases were sampled, DNA extracted, and sequenced using an Illumina TSO500HT cancer panel.",{"name":120,"@type":111,"acceptedAnswer":121},"Which gene was most commonly mutated, and how did TP53 findings differ among patients?",{"text":122,"@type":114},"TP53 was the most frequently mutated gene, altered in 65% of all samples; only two patients had no TP53 mutation in any sampled region.",{"name":124,"@type":111,"acceptedAnswer":125},"What do the results suggest about field cancerization and clonal selection?",{"text":126,"@type":114},"Malignant mutations in morphologically normal mucosa and surrounding dysplasia support field cancerization, while a lower average tumor mutational burden in lymph node metastases supports clonal selection.","https://schema.org",{"og:url":83,"og:type":129,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":131,"canonical":83},"index,follow",{"doc_id":133,"site_id":62},328990,1790505953,{"code":4,"msg":5,"data":136},{"doc_id":133,"user_id":137,"nickname":92,"user_avatar":138,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":139,"file_id":140,"file_url":141,"file_type":142,"file_size":143,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":144,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":67,"update_tm":148,"read_time":149},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","TYPE Original Research PUBLISHED 11 September 2024 DOI 10.3389/fonc.2024.1450361  \nOPEN ACCESS  \nEDITED BY  \nPeter Polverini,  \nUniversity of Michigan, United States  \nREVIEWED BY  \nEliska Svastova,  \nSlovak Academy of Sciences, Slovakia Stephen B. Keysar,  \nUniversity of Colorado Anschutz Medical Campus, United States  \n*CORRESPONDENCE Jakob Myllerup Jensen  \n [Jakob.myllerup.jensen@regionh.dk](Jakob.myllerup.jensen@regionh.dk)  \nRECEIVED 17 June 2024  \nACCEPTED 22 August 2024  \nPUBLISHED 11 September 2024  \nCITATION  \nJensen JM, Sjöstedt SMS, Carmona JL, Ahlborn LB, Vieira FG, Nielsen FC, Kiss K, Grønhøj C and von Buchwald C (2024) Genomic alterations in the stepwise progression from normal mucosa to metastasizing oral squamous cell carcinoma. Front. Oncol. 14:1450361 .  \ndoi: 10.3389/fonc.2024.1450361  \nCOPYRIGHT  \n© 2024 Jensen, Sjöstedt, Carmona, Ahlborn, Vieira, Nielsen, Kiss, Grønhøj and von Buchwald. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nGenomic alterations in the stepwise progression from normal mucosa to metastasizing oral squamous cell carcinoma  \nJakob Myllerup Jensen 1*, Sannia Mia Svenningsen Sjöstedt 1,2,3, Javiera Laing Carmona 4, Lise Barlebo Ahlborn 4,  \nFilipe Garrett Vieira 4, Finn Cilius Nielsen 4, Katalin Kiss 5, Christian Grønhøj 1 and Christian von Buchwald 1  \n1 Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, 2 Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, 3 Department Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark, 4 Department of Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, 5 Department of Pathology,  \nRigshospitalet, University of Copenhagen, Copenhagen, Denmark  \nIntroduction: The aim of this study was to investigate the genomic changes that occur in the development from dysplasia, cancer and to regional metastases inpatients with oral cavity squamous cell carcinoma (OSCC) .  \nMaterial and methods: We included OSCC patients with lymph node metastases at diagnosis, treated with primary surgery at Rigshospitalet, University of Copenhagen in the period 2007-2014 . The resected tumor specimens were evaluated by a pathologist, who marked areas of morphologically normal tissue and dysplasia surrounding the cancer, two areas from the cancer tissue, and one area within the lymph node metastases. From these areas a punch biopsy was taken, and DNA from each sample was extracted and sequenced using Illumina’sTSO500HT cancer panel.  \nResults: From 51 OSCC patients, 255 samples were included, comprising a wide variety of genomic alterations. Substantial intratumor heterogeneity was found. The most commonly mutated gene was TP53, mutated in 65% of all samples. Only two patients had no TP53 mutation in any samples. We found that morphologically normal appearing mucosa as well as surrounding dysplasia also contained malignant mutations, supporting the theory of field cancerization. There was a significant lower average tumor mutational burden (TMB) in the lymph node metastases compared to the primary tumors, supporting the theory of clonal selection.  \nConclusion: Substantial inter- and intratumor genomic heterogeneity was found. Mutation of TP53 was the most common and was present in all but two patients. Our data strongly supports the theory of clonal selection and the theory of field cancerization.  \nKEYWORDS  \nor","cbCaib73cfI6aavz","https://ap.wps.com/l/cbCaib73cfI6aavz","pdf",2165178,"English","# Introduction\n# Material and methods\n# Results\n# Conclusion","[{\"question\":\"What was the aim of the study on OSCC progression?\",\"answer\":\"To investigate genomic changes occurring from dysplasia and morphologically normal mucosa to invasive OSCC and regional lymph node metastases.\"},{\"question\":\"How were patient samples collected and analyzed?\",\"answer\":\"Multiple tissue regions around the cancer, from cancer tissue, and within lymph node metastases were sampled, DNA extracted, and sequenced using an Illumina TSO500HT cancer panel.\"},{\"question\":\"Which gene was most commonly mutated, and how did TP53 findings differ among patients?\",\"answer\":\"TP53 was the most frequently mutated gene, altered in 65% of all samples; only two patients had no TP53 mutation in any sampled region.\"},{\"question\":\"What do the results suggest about field cancerization and clonal selection?\",\"answer\":\"Malignant mutations in morphologically normal mucosa and surrounding dysplasia support field cancerization, while a lower average tumor mutational burden in lymph node metastases supports clonal selection.\"}]","Genomic alterations in the stepwise progression from normal mucosa to metastasizing oral squamous cell carcinoma | PDF",1789981992,23]