[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-377709-105":59,"doc-detail-377709-en":134},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":127,"head_meta":129,"extra_data":131,"updated_unix":133},105,"en","clinical-and-genomic-features-of-non-small-cell-lung-cancer-occurring-in-families","Clinical and genomic features of non-small cell lung cancer occurring in families","","Background: Exposure to environmental carcinogens, such as smoking, drives non-small cell lung cancer (NSCLC) carcinogenesis, but genetic contributions may also be involved. Methods: Twenty-three NSCLC patients with first-degree relatives affected by NSCLC were enrolled, and exome analyses were performed on germline and somatic DNA for 17 cases. Results: Germline analysis highlighted a shared pathogenic DHODH variant, while somatic alterations frequently involved EGFR and TP53; family-specific mutational mechanisms and signatures were suggested. Conclusion: Combining environmental exposure data with genetic information is key to identifying family-specific combinations underlying lung tumorigenesis.",{"@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/clinical-and-genomic-features-of-non-small-cell-lung-cancer-occurring-in-families/377709/",{"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/clinical-and-genomic-features-of-non-small-cell-lung-cancer-occurring-in-families/377709.png","ImageObject",300,407,{"name":92,"@type":93},"Olivia Brown","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main goal of the study?","Question",{"text":112,"@type":113},"To identify candidate tumor suppressor genes and characterize clinical and genomic features of NSCLC occurring within families.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were genetic analyses performed in the study?",{"text":117,"@type":113},"Exome analyses were conducted for both germline and somatic DNA using NSCLC specimens, with germline exome data analyzed for 17 cases.",{"name":119,"@type":110,"acceptedAnswer":120},"Which gene variant was shared among a pair of patients in the same family?",{"text":121,"@type":113},"A nonsynonymous DHODH variant, p.A347T, was shared and is a known pathogenic variant associated with Miller syndrome.",{"name":123,"@type":110,"acceptedAnswer":124},"What did the study suggest about mutational processes across families?",{"text":125,"@type":113},"Principal component analysis and mutational signature analysis indicated unique somatic SNV mechanisms in each family, including signatures consistent with DNA repair defects and ultraviolet exposure.","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},377709,1790472423,{"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":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":143,"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},16904993612988,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","DOI: 10.1111/1759-7714.14825  \nORIGINA L ARTICLE  \nClinical and genomic features of non-small cell lung cancer occurring in families  \nShingo Miyabe 1,2 | Shin Ito 3 | Ikuro Sato 4 | Jiro Abe 1,5 | Keiichi Tamai 5 | Mai Mochizuki 5 | Haruna Fujimori 5 | Kazunori Yamaguchi 3 | Norihisa Shindo 3 | Hiroshi Shima 6  | Tomoko Yamazaki 3 | Makoto Abue 5 | Yoshinori Okada 2 | Jun Yasuda 3   \n1Division of Thoracic Surgery, Miyagi Cancer Center Hospital, Natori, Japan 2Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan  \n3Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, Japan  \n4Division of Pathology, Miyagi Cancer Center Hospital, Natori, Japan  \n5Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori, Japan 6Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Natori, Japan  \nCorrespondence  \nJun Yasuda, Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute,  \n47-1 Nodayama, Medeshima Shiode, Natori, Miyagi 981-1293, Japan. [Email:](Email: jun-ysauda@miyagi-pho.jp)[ jun-ysauda@miyagi-pho.jp](Email: jun-ysauda@miyagi-pho.jp)  \nPresent address  \nJun Yasuda, Department of Head and Neck Oncology, Saitama Medical University International Medical Center, Saitama, Japan.  \nFunding information  \nMinistry of Education, Culture, Sports, Science and Technology > Japan Society for the Promotion of Science, Grant/Award Numbers: JP17K07187, JP18K09363, JP19K08430, JP19K09295, JP20K07436, JP21K07111, JP21K09665,  \nJP21K15495, JP22K07313  \nAbstract  \nBackground: Exposure to environmental carcinogens, such as through smoking, is a major factor in the carcinogenesis of non-small cell lung cancer (NSCLC) . However, genetic factors may also contribute.  \nMethods: To identify candidate tumor suppressor genes for NSCLC, we included 23 patients (10 related pairs and 3 individuals) with NSCLC who had other NSCLC-affected first-degree relatives in a local hospital. Exome analyses for both germline and somatic (NSCLC specimens) DNA were performed for 17 cases. Germline exome data of these 17 cases revealed that most of the short variants were identical to the variants in 14KJPN (a Japanese reference genome panel of more than 14 000 individuals) and only a nonsynonymous variant in the DHODH gene, p.A347T, was shared between a pair of NSCLC patients in the same family. This variant is a known pathogenic variant of the gene for Miller syndrome.  \nResults: Somatic genetic alterations in the exome data of our samples showed frequent mutations in the EGFR and TP53 genes. Principal component analysis of the patterns of 96 types of single nucleotide variants (SNVs) suggested the existence of unique mechanisms inducing somatic SNVs in each family. Delineation of mutational signatures of the somatic SNVs with deconstructSigs for the pair of germline pathogenic DHODH variant-positive cases showed that the mutational signatures of these cases included SBS3 (homologous recombination repair defect), SBS6, 15 (DNA mismatch repair), and SBS7 (ultraviolet exposure), suggesting that disordered pyrimidine production causes increased errors in DNA repair systems in these cases.  \nConclusion: Our results suggest the importance of the detailed collection of data on environmental exposure along with genetic information on NSCLC patients to identify the unique combinations that cause lung tumorigenesis in a particular family.  \nKEYW ORD S  \nDHODH, exome, mutational signature, non-small cell lung cancer, tumor suppressor gene  \nINTRODUCTION  \nNon-small cell lung cancer (NSCLC) is a leading cause of cancer death in Japan and worldwide (Cancer Statistics. Cancer Information Service, National Cancer Center, Japan  \n[Vital Statistics of Japan, Ministry of Health, Labour and Welfare]) . Environmental/behavioral factors such as smoking play critical roles in the tumorigenesis of NSCLC.1 Genetic factors are also wid","cbCaiqI4KiK3XFeE","https://ap.wps.com/l/cbCaiqI4KiK3XFeE","pdf",2835546,13,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Introduction","[{\"question\":\"What was the main goal of the study?\",\"answer\":\"To identify candidate tumor suppressor genes and characterize clinical and genomic features of NSCLC occurring within families.\"},{\"question\":\"How were genetic analyses performed in the study?\",\"answer\":\"Exome analyses were conducted for both germline and somatic DNA using NSCLC specimens, with germline exome data analyzed for 17 cases.\"},{\"question\":\"Which gene variant was shared among a pair of patients in the same family?\",\"answer\":\"A nonsynonymous DHODH variant, p.A347T, was shared and is a known pathogenic variant associated with Miller syndrome.\"},{\"question\":\"What did the study suggest about mutational processes across families?\",\"answer\":\"Principal component analysis and mutational signature analysis indicated unique somatic SNV mechanisms in each family, including signatures consistent with DNA repair defects and ultraviolet exposure.\"}]","Clinical and genomic features of non-small cell lung cancer occurring in families | PDF",1790226779,33]