title: Aberrant DNA methylation of acute myeloid leukemia and colorectal cancer in a Chinese pedigree with a MLL3 germline mutation.
abstract: 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.
authors.affiliation: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Fuhua
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Hematology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gong
authors.affiliation: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Hematology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Yunding
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Fengjiang
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of Hematology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Hematology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China. chenjpxn@163.com.
authors.forename: Jieping
authors.initials: J
authors.lastname: Chen
authors.affiliation: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China. liweidong98@tijmu.edu.cn.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Li
mesh_terms: D000328:Adult; D015179:Colorectal Neoplasms / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D010375:Pedigree
chemical_list: D004268:DNA-Binding Proteins; C452979:KMT2C protein, human
keywords: Acute myeloid leukemia; Colorectal cancer; DNA methylation