title: DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status.
abstract: In an initial epigenetic characterization of diffuse large B-cell lymphoma (DLBCL), we evaluated the DNA methylation levels of over 500 CpG islands. Twelve CpG islands (AR, CDKN1C, DLC1, DRD2, GATA4, GDNF, GRIN2B, MTHFR, MYOD1, NEUROD1, ONECUT2 and TFAP2A) showed significant methylation in over 85% of tumors. Interestingly, the methylation levels of a CpG island proximal to FLJ21062 differed between the activated B-cell-like (ABC-DLBCL) and germinal center B-cell-like (GCB-DLBCL) subtypes. In addition, we compared the methylation and expression status of 67 genes proximal (within 500 bp) to the methylation assays. We frequently observed that hypermethylated CpG islands are proximal to genes that are expressed at low or undetectable levels in tumors. However, many of these same genes were also poorly expressed in DLBCL tumors where their cognate CpG islands were hypomethylated. Nevertheless, the proportional reductions in BNIP3, MGMT, RBP1, GATA4, IGSF4, CRABP1 and FLJ21062 expression with increasing methylation suggest that epigenetic processes strongly influence these genes. Lastly, the moderate expression of several genes proximal to hypermethylated CpG tracts suggests that DNA methylation assays are not always accurate predictors of gene silencing. Overall, further investigation of the highlighted CpG islands as potential clinical biomarkers is warranted.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Pike
authors.forename: T C
authors.initials: TC
authors.lastname: Greiner
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: D D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Y-H
authors.initials: YH
authors.lastname: Hsu
authors.forename: G
authors.initials: G
authors.lastname: Renaud
authors.forename: T G
authors.initials: TG
authors.lastname: Wolfsberg
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.forename: D J
authors.initials: DJ
authors.lastname: Weisenberger
authors.forename: K D
authors.initials: KD
authors.lastname: Siegmund
authors.forename: W
authors.initials: W
authors.lastname: Ye
authors.forename: S
authors.initials: S
authors.lastname: Groshen
authors.forename: R
authors.initials: R
authors.lastname: Mehrian-Shai
authors.forename: J
authors.initials: J
authors.lastname: Delabie
authors.forename: W C
authors.initials: WC
authors.lastname: Chan
authors.forename: P W
authors.initials: PW
authors.lastname: Laird
authors.forename: J G
authors.initials: JG
authors.lastname: Hacia
mesh_terms: D035843:Biomedical Research / Q000592:standards; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins