{"created":"2023-07-27T06:58:26.165611+00:00","id":56816,"links":{},"metadata":{"_buckets":{"deposit":"d6bc8f9d-63fe-4ecc-a3dd-0319f2a83aed"},"_deposit":{"created_by":18,"id":"56816","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"56816"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00056816","sets":["2812:2813:2828"]},"author_link":["22226","25474"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2010-02-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"2p.","bibliographicVolumeNumber":"2004 – 2005","bibliographic_titles":[{"bibliographic_title":"平成17(2005)年度 科学研究費補助金 基盤研究(C) 研究成果報告書概要"},{"bibliographic_title":"2005 Fiscal Year Final Research Report Summary","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"本研究費によりこれまでに、子宮体癌におけるMLH1のメチル化に伴う蛋白発現の低下、および遺伝子不安定性に伴う下流遺伝子の変異について確認しており、さらに得られた成果を以下に示す。\n1.子宮内膜増殖症におけるMLH1プロモーターのメチル化解析\n子宮体癌の前癌病変である子宮内膜増殖症では、これまで得られる組織が極めて微量であったためメチル化解析法を行うことは困難であったが、制限酵素処理とBisulfite modificationの後に行うPCR反応を工夫することにより、微量組織からのMLH1プロモーターのメチル化解析が可能となった。その結果、子宮内膜増殖症27例のうち11例(41%)がメチル化を認め、子宮体癌とほぼ同等のメチル化頻度であることが確認された。\n2.PTEN変異との関連\n癌抑制遺伝子PTENは、子宮体癌の早期に変異を受けることが報告されている。同様に発癌の早期に関与するMLH1プロモーターメチル化との関連を調べた結果、PTEN変異は子宮体癌の38%、子宮内膜増殖症では19%に認められた。特に子宮内膜増殖症ではより異型度の強い複雑型増殖症により多くPTEN変異を認め、MLH1のメチル化は組織学的変化に先行し、その下流にPTEN変異が起こるという仮説が実証された。\n3.細胞診検体由来のメチル化、変異の解析\n本研究では、細胞診など形態学的変化と遺伝子診断を組み合わせた婦人科癌の早期診断を目的としてきた。これまでの予備実験でも、子宮内膜細胞診の際にスライドグラスに塗沫した後の残りの細胞を回収し、メチル化と変異の解析が十分可能であることが確認できた。しかし健常者でのメチル化と変異の頻度はそれほど高くないため、今後スクリーニングにおいて発癌リスクの高い症例を識別する臨床応用には、さらに症例数を増やして研究を進める必要があると考えている。","subitem_description_type":"Abstract"},{"subitem_description":"We already reported the methylation of MLH1 promoter and the decrease of its protein expression in endometrial cancer, and the mutations of downstream genes with microsatellite instabilities. With this funds, we provided more details as shown.\n1. Analysis of MLH1 promoter methylation in endometrial hyperplasia\nBecause of a very small amount for clinical sample of the endometrium hyperplasia, as a cancer precursor, it was difficult to perform methylation analysis. We developed the method of methylation analysis of the MLH1 promoter from the very small amount of endometrial sample, using PCR after restriction enzyme processing and Bisulfite modification. As a result, 11 of 27 endometrial hyperplasia examples (41%) were methylated, and the methylation frequency was approximately equal with endometrial cancers.\n2. Relation with the PTEN mutation\nPTEN is a cancer suppressor gene which has mutations in the early stage of endometrial cancers. As a result of PTEN mutation analysis, 38% of the endometrial cancers and 19% of the endometrial hyperplasias have PTEN mutations. We also found complex hyperplasias have more frequent PTEN mutations than simple hyperplasias. We recognize the methylation of MLH1 promoter is upstream of histological changes, and the PTEN mutation is a next step.\n3. The methylation and mutation analysis with cytological specimen\nIn this study, the purpose is gynecologic cancer screening with the combination of cyto-histology and genetic analysis. With our preliminary experiments, cytological specimen has enough samples for methylation and mutation analysis. In future, we have to distinguish the high risk patients for gynecologic carcinogenesis with methylation and mutation analysis of cytological specimens for clinical application.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:16591649, 研究期間(年度):2004 – 2005","subitem_description_type":"Other"},{"subitem_description":"出典：「DNA修復遺伝子のメチル化解析による婦人科癌早期診断への応用」研究成果報告書　課題番号16591649\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所））\n（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-16591649/165916492006kenkyu_seika_hokoku_gaiyo/)を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学医学部附属病院","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00063090","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://nrid.nii.ac.jp/ja/search/?kw=30303308"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://nrid.nii.ac.jp/ja/search/?kw=30303308","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-16591649/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-16591649/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-16591649/165916492006kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-16591649/165916492006kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-11-08"}],"displaytype":"detail","filename":"HO-PR-KANAYA-T-kaken 2010-2p.pdf","filesize":[{"value":"85.4 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"HO-PR-KANAYA-T-kaken 2010-2p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/56816/files/HO-PR-KANAYA-T-kaken 2010-2p.pdf"},"version_id":"68fe22b7-ea3b-44d2-af3b-482c14dc01fb"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"DNA修復遺伝子のメチル化解析による婦人科癌早期診断への応用","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"DNA修復遺伝子のメチル化解析による婦人科癌早期診断への応用"},{"subitem_title":"Analysis of Mismatch repair gene methylation for Gynecologic cancer screening","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2828"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-11-08"},"publish_date":"2021-11-08","publish_status":"0","recid":"56816","relation_version_is_last":true,"title":["DNA修復遺伝子のメチル化解析による婦人科癌早期診断への応用"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:25:22.429942+00:00"}