Aberrant DNA methylation of acute myeloid leukemia and colorectal cancer in a Chinese pedigree with a MLL3 germline mutation
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Unlike genetic aberrations, epigenetic alterations do not modify the deoxyribonucleic acid (DNA) coding sequence and can be reversed pharmacologically. Identifying a particular epigenetic alteration such as abnormal DNA methylation may provide better understanding of cancers and improve current therapy. In a Chinese pedigree with colorectal carcinoma and acute myeloid leukemia, we examined the genome-wide DNA methylation level of cases and explored the role of methylation in pathogenesis and progression. DNA methylation status in the four cases, which all harbor a MLL3 germline mutation, differed from that of the normal control, and hypermethylation was more prevalent. Also, more CpG sites were hypermethylated in the acute-phase AML patient than in the AML patient in remission. Fifty-nine hyper- or hypomethylated genes were identified as common to all four cases. Genome-wide DNA methylation analysis demonstrated that differentially methylated sites among acute myeloid leukemia and colorectal carcinoma cases and the control were in both promoters (CpG island) and gene body regions (shelf/shore areas). Hypermethylation was more prevalent in cancer cases. The study supports the suggestion that the level of DNA methylation changes in AML progression.
KeywordsAcute myeloid leukemia Colorectal cancer DNA methylation
We thank all subjects who donated blood samples for genetic research purposes. This work was supported in part by grant 81070576 from the National Natural Science Foundation of China and grant 12JCZDJC24700 from Tianjin Municipal Science and Technology Commission to W.-D.L.; and by National Natural Science Foundation of China (NSFC 81270605,30971066,81470324), Third Military Medical University Clinical and Science Great Fund Project (2102XLC03), Chongqing Postgraduate Education Reform Project (yjg123114), Chongqing Natural Science Fund Project (CSTC’2008BA5001), and Military Emphasis Medical Scientific Research Project Fund to J.-P.C.
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Conflicts of interest
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