{"created":"2023-06-20T15:49:10.768272+00:00","id":3747,"links":{},"metadata":{"_buckets":{"deposit":"75aa6009-c2ae-45b1-820f-bb5ad0a3e208"},"_deposit":{"created_by":4,"id":"3747","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"3747"},"status":"published"},"_oai":{"id":"oai:hama-med.repo.nii.ac.jp:00003747","sets":["2:15:17"]},"author_link":["11040"],"control_number":"3747","item_5_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"CCNB2とAURKAの過剰発現はTP53体細胞変異を有する日本人コルチゾール産生副腎皮質がんにおいて異常核分裂像を惹起する可能性がある","subitem_alternative_title_language":"ja"}]},"item_5_biblio_info_5":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-04-14","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"4","bibliographicPageStart":"e0231665","bibliographicVolumeNumber":"15","bibliographic_titles":[{"bibliographic_title":"PLOS ONE","bibliographic_titleLang":"en"}]}]},"item_5_date_granted_17":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2021-03-16"}]},"item_5_degree_grantor_15":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"浜松医科大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"13802","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_12":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_5_description_13":{"attribute_name":"学位の区分","attribute_value_mlt":[{"subitem_description":"doctoral","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_5_description_14":{"attribute_name":"学位の分野","attribute_value_mlt":[{"subitem_description":"医学系研究科","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_5_description_9":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background\nMany genomic analyses of cortisol-producing adrenocortical carcinoma (ACC) have been reported, but very few have come from East Asia. The first objective of this study is to verify the genetic difference with the previous reports by analyzing targeted deep sequencing of 7 Japanese ACC cases using next-generation sequencing (NGS). The second objective is to compare the somatic variant findings identified by NGS analysis with clinical and pathological findings, aiming to acquire new knowledge about the factors that contribute to the poor prognosis of ACC and to find new targets for the treatment of ACC.\nMethod\nDNA was extracted from ACC tissue of seven patients and two reference blood samples. Targeted deep sequencing was performed using the MiSeq system for 12 genes, and the obtained results were analyzed using MuTect2. The hypothesis was obtained by integrating the somatic variant findings with clinical and pathological data, and it was further verified using The Cancer Genome Atlas (TCGA) dataset for ACC.\nResults\nSix possible pathogenic and one uncertain significance somatic variants including a novel PRKAR1A (NM_002734.4):c.545C>A (p.T182K) variant were found in five of seven cases. By integrating these data with pathological findings, we hypothesized that cases with TP53 variants were more likely to show atypical mitotic figures. Using TCGA dataset, we found that atypical mitotic figures were associated with TP53 somatic variant, and mRNA expression of CCNB2 and AURKA was significantly high in TP53 mutated cases and atypical mitotic figure cases.\nConclusion\nWe believe this is the first report that discusses the relationship between atypical mitotic figures and TP53 somatic variant in ACC. We presumed that overexpression of CCNB2 and AURKA mRNA may cause atypical mitosis in TP53 somatic mutated cases. Because AURKA is highly expressed in atypical mitotic cases, it may be an appropriate indicator for AURKA inhibitors.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_5_dissertation_number_18":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第865号"}]},"item_5_publisher_6":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Public Library of Science (PLoS)","subitem_publisher_language":"en"}]},"item_5_relation_26":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"32287321","subitem_relation_type_select":"PMID"}}]},"item_5_relation_28":{"attribute_name":"出版社DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1371/journal.pone.0231665","subitem_relation_type_select":"DOI"}}]},"item_5_rights_7":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"Copyright 2020 Ikeya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.","subitem_rights_language":"en"}]},"item_5_source_id_20":{"attribute_name":"EISSN","attribute_value_mlt":[{"subitem_source_identifier":"1932-6203","subitem_source_identifier_type":"EISSN"}]},"item_5_version_type_32":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"池谷, 章","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"11040","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-08-01"}],"displaytype":"detail","filename":"DT_865ronbun.pdf","filesize":[{"value":"1.9 MB"}],"format":"application/pdf","licensetype":"license_0","mimetype":"application/pdf","url":{"label":"論文本文","objectType":"fulltext","url":"https://hama-med.repo.nii.ac.jp/record/3747/files/DT_865ronbun.pdf"},"version_id":"c877d854-8132-4643-ae30-99a9552788e6"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"CCNB2 and AURKA overexpression may cause atypical mitosis in Japanese cortisol-producing adrenocortical carcinoma with TP53 somatic variant","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"CCNB2 and AURKA overexpression may cause atypical mitosis in Japanese cortisol-producing adrenocortical carcinoma with TP53 somatic variant","subitem_title_language":"en"}]},"item_type_id":"5","owner":"4","path":["17"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-08-01"},"publish_date":"2021-08-01","publish_status":"0","recid":"3747","relation_version_is_last":true,"title":["CCNB2 and AURKA overexpression may cause atypical mitosis in Japanese cortisol-producing adrenocortical carcinoma with TP53 somatic variant"],"weko_creator_id":"4","weko_shared_id":-1},"updated":"2023-11-13T07:39:45.941586+00:00"}