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Molecular drivers of genomic and transcriptomic alterations underlying this progression remain unclear in Indian oral squamous cell carcinoma (OSCC). Whole exome, copy-number, and transcriptome profiling across multi-regional tumors and dysplastic lesions, linked to in vitro validation, identifies early CASP8 alterations as initiating events and connects immune and mutational signatures to tumor development.",{"@graph":69,"@context":126},[70,84,105],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/multi-regional-genomic-and-transcriptomic-characterization-of-a-melanoma-associated-oral-cavity-cancer-brief-report/328833/",{"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/multi-regional-genomic-and-transcriptomic-characterization-of-a-melanoma-associated-oral-cavity-cancer-brief-report/328833.png","ImageObject",300,407,{"name":92,"@type":93},"Levi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"What is the clinical problem addressed in this study?","Question",{"text":112,"@type":113},"The study focuses on how precancerous and malignant lesions in the oral cavity evolve through field cancerization, and why the molecular genomic and transcriptomic events driving this process are still unclear in Indian OSCC patients.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were genomic and transcriptomic alterations measured?",{"text":117,"@type":113},"Whole exome sequencing, copy-number variation array, and whole transcriptome sequencing were performed on multiple tumors and dysplastic lesions from distinct anatomical subsites, with blood sampled from a rare OSCC patient.",{"name":119,"@type":110,"acceptedAnswer":120},"What role does CASP8 play according to the results?",{"text":121,"@type":113},"A missense CASP8 mutation (p. S375F) was observed as the initiating event in oral tumor field development, and pharmacological inhibition of CASP8 increased cellular migration and viability in a CASP8-wild type OSCC cell line.",{"name":123,"@type":110,"acceptedAnswer":124},"What do the authors conclude about tumor progression?",{"text":125,"@type":113},"CASP8 alterations are proposed as the earliest driving events in oral field carcinogenesis, while additional somatic mutational, copy number, and transcriptomic alterations contribute later to OSCC formation and progression.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},328833,1790842491,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":34,"language":143,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":144,"faqs":145,"seo_title":146,"seo_description":67,"update_tm":147,"read_time":148,"preview_page_count":4},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Chakravarty et al. Human Genomics (2024) 18:96 [https://doi.org/10.1186/s40246-024-00668-8](https://doi.org/10.1186/s40246-024-00668-8)  \nHuman Genomics  \n BRIEF REPORT Open Access  \nMulti-regional genomic and transcriptomic   characterization of a melanoma-associated oral cavity cancer provide evidence for CASP8 alteration-mediated field cancerization  \nShouvik Chakravarty1,2, Arnab Ghosh1,2, Chitrarpita Das 1, Subrata Das 1, Subrata Patra 1, Arindam Maitra 1, Sandip Ghose3* and Nidhan K Biswas1,2*  \nAbstract  \nBackground Precancerous and malignant tumours arise within the oral cavity from a predisposed “field” of epithelial cells upon exposure to carcinogenic stimulus. This phenomenon is known as“Field Cancerization”. The molecular genomic and transcriptomic alterations that lead to field cancerization and tumour progression is unknown in Indian Oral squamous cell carcinoma (OSCC) patients.  \nMethods We have performed whole exome sequencing, copy-number variation array and whole transcriptome sequencing from five tumours and dysplastic lesions (sampled from distinct anatomical subsites-one each  \nfrom buccal anterior and posterior alveolus, dorsum of tongue–mucosal melanoma, lip and left buccal mucosa) and blood from a rare OSCC patient with field cancerization.  \nResults A missense CASP8 gene mutation (p. S375F) was observed to be the initiating event in oral tumour  \nfield development. APOBEC mutation signatures, arm-level copy number alterations, depletion of CD8 + T cells and activated NK cells and enrichment of pro-inflammatory mast cells were features of early-originating tumours. Pharmacological inhibition of CASP8 protein in a CASP8-wild type OSCC cell line showed enhanced levels of cellular migration and viability.  \nConclusion CASP8 alterations are the earliest driving events in oral field carcinogenesis, whereas additional somatic mutational, copy number and transcriptomic alterations ultimately lead to OSCC tumour formation and progression. Keywords Field cancerization, OSCC, CASP8, APOBEC, CD8 +T cells, Immune checkpoint  \nIntroduction  \nOral squamous cell carcinoma (OSCC) is one of the topmost health threats in India [1]. Under the influence of carcinogenic stimulants (smokeless tobacco) [2], normal  \n*Correspondence:  \nSandip Ghose [sanindra1967@gmail.com](sanindra1967@gmail.com)[ ](sanindra1967@gmail.com)Nidhan K Biswas[nkb1@nibmg.ac.in](nkb1@nibmg.ac.in)  \nFull list of author information is available at the end of the article  \noral epithelia develop dysplasia and over a period of time accumulate pro-tumorigenic alterations. This gives rise to a localized cancerous “patch” (field cancerization). In head and neck squamous cell cancer (HNSCC), the cancerized field may stretch over an area having a diameter of up to 7 cm. In a clinico-pathological study by Slaughter et al. [3]. involving 783 OSCC cases, ~ 20% of the patients harbored a secondary lesion (precancerous or malignant) in addition to their primary tumours. Due to morphologically indistinguishable changes, histopathological  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyr","cbCaim67ljb2dGT9","https://ap.wps.com/l/cbCaim67ljb2dGT9","pdf",2767692,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Introduction","[{\"question\":\"What is the clinical problem addressed in this study?\",\"answer\":\"The study focuses on how precancerous and malignant lesions in the oral cavity evolve through field cancerization, and why the molecular genomic and transcriptomic events driving this process are still unclear in Indian OSCC patients.\"},{\"question\":\"How were genomic and transcriptomic alterations measured?\",\"answer\":\"Whole exome sequencing, copy-number variation array, and whole transcriptome sequencing were performed on multiple tumors and dysplastic lesions from distinct anatomical subsites, with blood sampled from a rare OSCC patient.\"},{\"question\":\"What role does CASP8 play according to the results?\",\"answer\":\"A missense CASP8 mutation (p. S375F) was observed as the initiating event in oral tumor field development, and pharmacological inhibition of CASP8 increased cellular migration and viability in a CASP8-wild type OSCC cell line.\"},{\"question\":\"What do the authors conclude about tumor progression?\",\"answer\":\"CASP8 alterations are proposed as the earliest driving events in oral field carcinogenesis, while additional somatic mutational, copy number, and transcriptomic alterations contribute later to OSCC formation and progression.\"}]","Multi-regional genomic and transcriptomic characterization of a melanoma-associated oral cavity cancer - Brief report | PDF",1789981251,18]