{"created":"2023-07-27T06:54:59.550256+00:00","id":50605,"links":{},"metadata":{"_buckets":{"deposit":"2de21b1c-3357-4aef-bf63-af265cbe9d87"},"_deposit":{"created_by":18,"id":"50605","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"50605"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00050605","sets":["2812:2813:2830"]},"author_link":["91613","20086"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2005-04-18","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"2p.","bibliographicVolumeNumber":"2001-2003","bibliographic_titles":[{"bibliographic_title":"平成15(2003)年度 科学研究費補助金 基盤研究(B) 研究成果報告書概要"},{"bibliographic_title":"2003 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":"子宮体癌の発生には遺伝子不安定性(MSI : microsatellite instability)がハブ機能を有すると考えられる。MSI状態に導く遺伝子はDNAミスマッチ修復遺伝子の機能障害である。DNA修復遺伝子の機能障害は体癌ではMLH1の発現異常が重要で、MLH1蛋白発現の低下は遺伝子の変異ではなくプロモーターの過剰なメチル化が原因である。メチル化の検出にはmethylation specific PCR法およびbisulfite sequence法を用いた。これによるとMLH1の蛋白発現はプロモーターのCpGに富む領域のメチル化と極めて高い相関を示した。体癌組織の約30%の症例に80%以上の、50%以上の症例に10%以上のCpG領域でのメチル化が見られた。正常内膜ではメチル化は皆無であったが、過剰メチル化のある体癌周辺の正常内膜組織では約30%に過剰なメチル化が進行していた。内膜増殖症でも癌と同じ程度にメチル化がみられた。MLH1の過剰メチル化症例ではMSI及びTGF- βReceptor typeIIやPTENのフレームシフト変異が有為に高率であった。更に蛋白発現をみると癌周囲の正常内膜にも蛋白の消失が見られ,内膜の形態変化よりも早期にMLH1プロモーターのメチル化が進行すると考えられた。従って、MLHIプロモーターは発癌の過程では最も早期に起こる変化であると言える。このようなエピジェネチック変化を、特に子宮体癌ではMLHIプロモーターのメチル化を早期診断やリスク因子選別のための分子標的として捕らえることができる。MSIの結果として生じるPTEN, TGF-β-RII、p53、Ras等の遺伝子変異や発現も分子標的としてDNAチップなどで網羅的に検出し癌の診断に応用可能である。これらを総合的に診断することにより高リスクの個人や癌の早期診断に臨床応用の可能性が示された。その他の、癌の早期発見の分子標的としてテロメラーゼ活性も期待が持てる。すなわち、テロメラーゼ活性が95%以上の癌細胞に認められ、微量検体にて子宮体癌や頚部癌の診断に臨床応用可能である。癌の診断や術後の経過観察の腫瘍マーカー分子としても臨床応用可能である。","subitem_description_type":"Abstract"},{"subitem_description":"Silencing of the MLH1 gene by promoter hypermethylation is the main mechanism underlying the microsatellite instability(MSI) phenotype in endometrial cancers. MSI has a key role in the endometrial carcinogesis where mutations of multiple genes have involved.\nWe have developed the convenient and sensitive method for the detection of promoter hypermethylation in the region 700bp upstream of MLH1 covering 48 CpG sites. The metylation of these sites has been confirmed by bisulfate sequencing. Metylation status was classified as full(over 80% of CpGs are methylated), partial(10-80%) or nonmethylation(less than 10%). Of endometrial cancers examined, 30% were fully methylated, 25% were partially methylated and 45% were not methylated. Analysis of MLH1 by immunohistochemical methods and of MSI revealed that the degree, rather than region-specific methylation of CpG island is critical for decreased MLH1 expression and the MSI phenotype. Among patients with methylated cancers, almost half patients have contained methylated promoters in their normal endometria with profiles similar to those of cancerous lesions, and these were closely associated with the MSI phenotype. In contrast, only a few cases of normal endometria from patients without endometrial malignancies harbored methylated promoters. The present study suggests that hypermetylation of the MLH1 promoter is frequent in the histologically-cofirmed normal endometrium adjacent to cancerous lesions, supporting the notion that hypermethylation of DNA-mismatch repair genes is the initial step that triggers the following various genetic events in the endometrial carcinogenesis. Of course, the genetic events could be candidates for molecular targets in the diagnosis and treatment.\nDetection of some molecular targets in a tiny clinical sample might be a useful diagnostic aid in cancer screening.","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:13557137, 研究期間(年度):2001-2003","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「遺伝子変異メチル化の定量的検出法の開発と子宮内膜癌発生予知への臨床応用」課題番号13557137\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/report/KAKENHI-PROJECT-13557137/135571372003kenkyu_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":"金沢大学医薬保健研究域医学系","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00056914","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://kaken.nii.ac.jp/search/?qm=10127186"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=10127186","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13557137/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13557137/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-13557137/135571372003kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-13557137/135571372003kenkyu_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":"2022-04-25"}],"displaytype":"detail","filename":"ME-PR-INOUE-M-kaken 2005-3p.pdf","filesize":[{"value":"122.8 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-INOUE-M-kaken 2005-3p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/50605/files/ME-PR-INOUE-M-kaken 2005-3p.pdf"},"version_id":"8b857804-9ca5-4432-823c-3260ddac0d09"}]},"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":"遺伝子変異メチル化の定量的検出法の開発と子宮内膜癌発生予知への臨床応用","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"遺伝子変異メチル化の定量的検出法の開発と子宮内膜癌発生予知への臨床応用"},{"subitem_title":"Detection of the hypennethylation of MLH1 promoter and its clinical application in endometrial cancer screening","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2830"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-04-25"},"publish_date":"2022-04-25","publish_status":"0","recid":"50605","relation_version_is_last":true,"title":["遺伝子変異メチル化の定量的検出法の開発と子宮内膜癌発生予知への臨床応用"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T13:08:38.998281+00:00"}