https://scholars.lib.ntu.edu.tw/handle/123456789/537460
標題: | Distinct association between aberrant methylation of Wnt inhibitors and genetic alterations in acute myeloid leukaemia | 作者: | HSIN-AN HOU Kuo Y.-Y. Liu C.-Y. Lee M.C. JIH-LUH TANG Chen, Chien-Yuan WEN-CHIEN CHOU Huang C.-F. Lee F.-Y. Liu M.-C. MING YAO HWEI-FANG TIEN |
公開日期: | 2011 | 卷: | 105 | 期: | 12 | 起(迄)頁: | 1927-1933 | 來源出版物: | British Journal of Cancer | 摘要: | Background: Aberrant activation of Wnt signalling through hypermethylation of Wnt inhibitor genes is involved in several human malignancies, including acute myeloid leukaemia (AML). It remains unclear whether hypermethylation of Wnt inhibitors is associated with molecular gene mutations in the development of AML. Methods: We investigated the association of the promoter hypermethylation of six Wnt inhibitors (Wif-1, SFRP1, SFRR2, SFRP4, SFRP5, and DKK1) with gene aberrations in the leukaemogenesis of 269 AML patients. Results: In total, 166 patients (61.7%) had hypermethylation of at least one Wnt inhibitor. The majority (68.5%) of patients with Wnt inhibitor hypermethylation had concurrent Class II gene mutations that affect transcription factors or cofactors. There was a close association of Wif-1 hypermethylation with t(15;17) (P0.0005) and CEBPA mutation (P0.0001), DKK1 hypermethylation with t(8;21) (P0.0001) and ASXL1 mutation (P0.0078), SFRP-1 hypermethylation with t(8;21) (P0.0001), SFRP-2 hypermethylation with AML1/RUNX1 mutation (P0.0012), and SFRP-5 hypermethylation with MLL/PTD (P0.0505). On the other side, hypermethylation of Wnt inhibitors was always negatively associated with NPM1 mutation and FLT3/ITD. Conclusion: There was distinct association between hypermethylation of individual Wnt inhibitors and specific gene aberrations, especially Class II mutations. The Wnt inhibitor hypermethylation might interact with genetic alterations in the leukaemogenesis. ? 2011 Cancer Research UK All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84855990101&doi=10.1038%2fbjc.2011.471&partnerID=40&md5=230cdf4208d593f922519b8eb81f8ace https://scholars.lib.ntu.edu.tw/handle/123456789/537460 |
ISSN: | 0007-0920 | DOI: | 10.1038/bjc.2011.471 | SDG/關鍵字: | CD11b antigen; CD135 antigen; CD14 antigen; CD19 antigen; CD34 antigen; CD7 antigen; dickkopf 1 protein; HLA DR antigen; lactate dehydrogenase; nucleophosmin; protein inhibitor; secreted frizzled related protein 1; secreted frizzled related protein 2; secreted frizzled related protein 4; secreted frizzled related protein 5; transcription factor RUNX1; unclassified drug; Wnt inhibitory factor 1; Wnt protein; Wnt protein; acute granulocytic leukemia; adolescent; adult; aged; antigen expression; article; controlled study; cytogenetics; female; gene mutation; genetic association; human; human cell; immunophenotyping; lactate dehydrogenase blood level; leukemogenesis; leukocyte count; major clinical study; male; priority journal; promoter region; protein methylation; sex difference; thrombocyte count; treatment response; DNA methylation; drug antagonism; genetics; immunology; mutation; pathology; polymerase chain reaction; Adult; DNA Methylation; Humans; Immunophenotyping; Leukemia, Myeloid, Acute; Mutation; Polymerase Chain Reaction; Wnt Proteins |
顯示於: | 醫學系 |
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