We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Distinct association between aberrant methylation of Wnt inhibitors and genetic alterations in acute myeloid leukaemia.
- Authors
Hou, H-A; Kuo, Y-Y; Liu, C-Y; Lee, M C; Tang, J-L; Chen, C-Y; Chou, W-C; Huang, C-F; Lee, F-Y; Liu, M-C; Yao, M; Tien, H-F
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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) (P=0.0005) and CEBPA mutation (P<0.0001), DKK1 hypermethylation with t(8;21) (P<0.0001) and ASXL1 mutation (P=0.0078), SFRP-1 hypermethylation with t(8;21) (P<0.0001), SFRP-2 hypermethylation with AML1/RUNX1 mutation (P=0.0012), and SFRP-5 hypermethylation with MLL/PTD (P=0.0505). On the other side, hypermethylation of Wnt inhibitors was always negatively associated with NPM1 mutation and FLT3/ITD.<bold>Conclusion: </bold>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.
- Subjects
ACUTE myeloid leukemia; MYELOID leukemia; GENES; METHYLATION; TRANSCRIPTION factors; GENETIC mutation; RESEARCH; RESEARCH methodology; MEDICAL cooperation; EVALUATION research; DNA methylation; COMPARATIVE studies; GLYCOPROTEINS; IMMUNOPHENOTYPING; POLYMERASE chain reaction; CHEMICAL inhibitors
- Publication
British Journal of Cancer, 2011, Vol 105, Issue 12, p1927
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/bjc.2011.471