{"created":"2023-05-15T14:50:42.313622+00:00","id":69339,"links":{},"metadata":{"_buckets":{"deposit":"16ec68eb-80aa-4a72-a38d-38fb4944f2d5"},"_deposit":{"created_by":1,"id":"69339","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"69339"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00069339","sets":["10:28"]},"author_link":["680471","680470","680475","680479","680480","680474","680469","680473","680481","680472","680476","680478","680477","680482"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2008-05-02","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Deficiencies in DNA mismatch repair (MMR) result in replication errors that cause frameshift mutations and/or point mutations within key tumor suppressor genes or oncogenes. Heterozygous germline mutations in MMR genes are the cause of hereditary nonpolyposis colorectal cancer (HNPCC). In these cancers, mutations in mononucleotide repeat sequences in TGFbRII, BAX, etc. have been frequently reported. Homozygous germline mutations of MMR genes, such as MLH1, MSH2 and PMS2, are also manifested by an early onset of childhood T- or B-cell leukemias, but the target gene was not identified yet. Analogous to the human phenotype, MMR deficient mice, Mlh1 and Msh2, develop aggressive lymphomas, which are predominantly of T-cell origin. These MMR-deficient lymphomas show a significant increase in both point mutations and microsatellite instability in the mononucleotide repeat sequences. In this study, we focused on the Ikaros, a master transcription factor of lymphoid lineage commitment and differentiation, as a target gene of Mlh1 deficiency and elucidated the frequency and spectrum of the mutation.\n  T-cell lymphomas of Mlh1-knockout mice developed either spontaneously or upon exposure to whole-body X-irradiation at 2 Gy. Expression of Ikaros and b-actin proteins was analyzed by western blotting. Ikaros mRNA was also analyzed its expression pattern by RT-PCR and sequenced.\n  Three quarters of lymphomas lacked Ikaros protein expression, which resulted from a frameshift mutation that created a stop codon. Mononucleotide repeat sequences at 1029–1034(C)6 and 1567–1572(G)6 in Ikaros were mutational hot spots with a one-base deletion occurring with a frequency of 45 and 50%, respectively. Point mutations and splicing alterations were also observed. In total, 85% of the lymphomas showed aberrations in Ikaros. The characteristic of Mlh1-deficient lymphomas is harboring of multiple mutations simultaneously in the same tumor, displaying a combination of two frameshift mutations at different repeats, frameshift and point mutations, and/or deletion mutations. This report indicates Ikaros mutations are coupled with Mlh1 deficiency in lymphomagenesis.","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"3rd CH/GOSH Childhood Leukaemia Symposium","subitem_description_type":"Other"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Kakinuma, Shizuko"}],"nameIdentifiers":[{"nameIdentifier":"680469","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kodama, Youtarou"}],"nameIdentifiers":[{"nameIdentifier":"680470","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Amasaki, Yoshiko"}],"nameIdentifiers":[{"nameIdentifier":"680471","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Takimoto, Misaki"}],"nameIdentifiers":[{"nameIdentifier":"680472","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nishimura, Mayumi"}],"nameIdentifiers":[{"nameIdentifier":"680473","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ariyoshi, Kentaro"}],"nameIdentifiers":[{"nameIdentifier":"680474","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Shimada, Yoshiya"}],"nameIdentifiers":[{"nameIdentifier":"680475","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"柿沼 志津子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680476","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"小玉 陽太郎","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680477","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"甘崎 佳子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680478","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"滝本 美咲","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680479","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"西村 まゆみ","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680480","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"有吉 健太郎","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680481","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"島田 義也","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"680482","nameIdentifierScheme":"WEKO"}]}]},"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":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"Ikaros is a mutational target for lymphomagenesis in Mlh1-deficient mice","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Ikaros is a mutational target for lymphomagenesis in Mlh1-deficient mice"}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2008-05-22"},"publish_date":"2008-05-22","publish_status":"0","recid":"69339","relation_version_is_last":true,"title":["Ikaros is a mutational target for lymphomagenesis in Mlh1-deficient mice"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T20:15:40.305603+00:00"}