{"created":"2023-05-15T09:41:14.039600+00:00","id":297,"links":{},"metadata":{"_buckets":{"deposit":"661e901f-d668-411b-8f7d-1e402b12b925"},"_deposit":{"created_by":11,"id":"297","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"297"},"status":"published"},"_oai":{"id":"oai:kagawa-u.repo.nii.ac.jp:00000297","sets":["13:40"]},"author_link":["445"],"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2018-03-24"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"香川大学"},{"subitem_degreegrantor_language":"en","subitem_degreegrantor_name":"Kagawa University"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"16201","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_10006_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Abstract\n\nThe recent development of next‐generation sequencing technology for extensive mutation analysis, and beadarray technology for genome‐wide DNA methylation analysis has made it possible to obtain integrated pictures of genetic and epigenetic alterations, using the same cancer samples. In this study, we aimed to characterize such a picture in esophageal squamous cell carcinomas (ESCCs). Base substitutions of 55 cancer‐related genes and copy number alterations (CNAs) of 28 cancer‐related genes were analyzed by targeted sequencing. Forty‐four of 57 ESCCs (77%) had 64 non‐synonymous somatic mutations, and 24 ESCCs (42%) had 35 CNAs. A genome‐wide DNA methylation analysis using an Infinium HumanMethylation450 BeadChip array showed that the CpG island methylator phenotype was unlikely to be present in ESCCs, a different situation from gastric and colon cancers. Regarding individual pathways affected in ESCCs, the WNT pathway was activated potentially by aberrant methylation of its negative regulators, such as SFRP1, SFRP2, SFRP4, SFRP5, SOX17, and WIF1 (33%). The p53 pathway was inactivated by TP53 mutations (70%), and potentially by aberrant methylation of its downstream genes. The cell cycle was deregulated by mutations of CDKN2A (9%), deletions of CDKN2A and RB1 (32%), and by aberrant methylation of CDKN2A and CHFR (9%). In conclusion, ESCCs had unique methylation profiles different from gastric and colon cancers. The genes involved in the WNT pathway were affected mainly by epigenetic alterations, and those involved in the p53 pathway and cell cycle regulation were affected mainly by genetic alterations.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10006_dissertation_number_12":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第676号"}]},"item_10006_relation_15":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1002/mc.22452","subitem_relation_type_select":"DOI"}},{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://dl.ndl.go.jp/pid/11122657","subitem_relation_type_select":"URI"}}]},"item_10006_relation_22":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"26756304","subitem_relation_type_select":"PMID"}}]},"item_10006_relation_28":{"attribute_name":"論文ID（NAID）","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"500001077629","subitem_relation_type_select":"NAID"}}]},"item_10006_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2016 Wiley Periodicals, Inc.","subitem_rights_language":"en"}]},"item_10006_text_30":{"attribute_name":"KEID","attribute_value_mlt":[{"subitem_text_value":"28447"}]},"item_10006_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_fa2ee174bc00049f","subitem_version_type":"P"}]},"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":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationName":"","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"Kishino, Takayoshi","creatorNameLang":"en"},{"creatorName":"岸野, 貴督","creatorNameLang":"ja"},{"creatorName":"キシノ, タカヨシ","creatorNameLang":"ja-Kana"}],"familyNames":[{"familyName":"Kishino","familyNameLang":"en"},{"familyName":"岸野","familyNameLang":"ja"},{"familyName":"キシノ","familyNameLang":"ja-Kana"}],"givenNames":[{"givenName":"Takayoshi","givenNameLang":"en"},{"givenName":"貴督","givenNameLang":"ja"},{"givenName":"タカヨシ","givenNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"445","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"8000001632079","nameIdentifierScheme":"CiNii ID","nameIdentifierURI":"http://ci.nii.ac.jp/nrid/8000001632079"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-10-30"}],"displaytype":"detail","filename":"Med_A676.pdf","filesize":[{"value":"2.1 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kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"審査の結果の要旨","objectType":"other","url":"https://kagawa-u.repo.nii.ac.jp/record/297/files/Med_A676_result.pdf"},"version_id":"0e8c4f1e-d8fc-46f7-a2c9-b80e908988b9"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"DNA methylation","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"cancer-related pathway","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"epigenetics","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"esophageal squamous cell carcinoma (ESCC)","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"genetic alterations","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"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":"Integrated analysis of DNA methylation and mutations in esophageal squamous cell carcinoma","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Integrated analysis of DNA methylation and mutations in esophageal squamous cell carcinoma","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"11","path":["40"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2018-05-30"},"publish_date":"2018-05-30","publish_status":"0","recid":"297","relation_version_is_last":true,"title":["Integrated analysis of DNA methylation and mutations in esophageal squamous cell carcinoma"],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2024-10-31T07:59:55.707660+00:00"}