Novel genes exhibiting DNA methylation alterations in Korean patients with chronic lymphocytic leukaemia: a methyl-CpG-binding domain sequencing study

• Published in: Scientific reports Vol. 10; no. 1; p. 1085
• Main Authors: Kim, Miyoung, Lee, Eunyup, Zang, Dae Young, Kim, Hyo Jung, Kim, Ho Young, Han, Boram, Kim, Han-Sung, Kang, Hee Jung, Hwang, Seungwoo, Lee, Young Kyung
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.01.2020; Nature Publishing Group
• Subjects: 45/23; 692/308/2056; 692/699/67/1990/283/1895; B-cell receptor; Chronic lymphocytic leukemia; Cohort Studies; CpG Islands; DNA Methylation; Epigenesis, Genetic; Female; Genes; Genomes; Grb2 protein; Humanities and Social Sciences; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Lymphocytes B; Male; Middle Aged; multidisciplinary; Mutation; Promoter Regions, Genetic; Republic of Korea; Science; Science (multidisciplinary); Signal transduction; Stat3 protein; Syk protein; Republic of Korea
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-57919-6

Chronic lymphocytic leukaemia (CLL) exhibits differences between Asians and Caucasians in terms of incidence rate, age at onset, immunophenotype, and genetic profile. We performed genome-wide methylation profiling of CLL in an Asian cohort for the first time. Eight Korean patients without somatic immunoglobulin heavy chain gene hypermutations underwent methyl-CpG-binding domain sequencing (MBD-seq), as did five control subjects. Gene Ontology, pathway analysis, and network-based prioritization of differentially methylated genes were also performed. More regions were hypomethylated (2,062 windows) than were hypermethylated (777 windows). Promoters contained the highest proportion of differentially methylated regions (0.08%), while distal intergenic and intron regions contained the largest number of differentially methylated regions. Protein-coding genes were the most abundant, followed by long noncoding and short noncoding genes. The most significantly over-represented signalling pathways in the differentially methylated gene list included immune/cancer-related pathways and B-cell receptor signalling. Among the top 10 hub genes identified via network-based prioritization, four ( UBC , GRB2 , CREBBP , and GAB2 ) had no known relevance to CLL, while the other six ( STAT3 , PTPN6 , SYK , STAT5B , XPO1 , and ABL1 ) have previously been linked to CLL in Caucasians. As such, our analysis identified four novel candidate genes of potential significance to Asian patients with CLL.