DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status

B. L. Pike, Timothy Charles Greiner, X. Wang, D. D. Weisenburger, Y. H. Hsu, G. Renaud, T. G. Wolfsberg, M. Kim, D. J. Weisenberger, K. D. Siegmund, W. Ye, S. Groshen, R. Mehrian-Shai, J. Delabie, W. C. Chan, P. W. Laird, J. G. Hacia

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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 500bp) 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.

Original languageEnglish (US)
Pages (from-to)1035-1043
Number of pages9
JournalLeukemia
Volume22
Issue number5
DOIs
StatePublished - Jan 1 2008

Fingerprint

CpG Islands
Lymphoma, Large B-Cell, Diffuse
DNA Methylation
Methylation
Gene Expression
Genes
B-Lymphocytes
Genetic Epigenesis
Glial Cell Line-Derived Neurotrophic Factor
Neoplasms
Germinal Center
Gene Silencing
Epigenomics
Biomarkers

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Pike, B. L., Greiner, T. C., Wang, X., Weisenburger, D. D., Hsu, Y. H., Renaud, G., ... Hacia, J. G. (2008). DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status. Leukemia, 22(5), 1035-1043. https://doi.org/10.1038/leu.2008.18

DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status. / Pike, B. L.; Greiner, Timothy Charles; Wang, X.; Weisenburger, D. D.; Hsu, Y. H.; Renaud, G.; Wolfsberg, T. G.; Kim, M.; Weisenberger, D. J.; Siegmund, K. D.; Ye, W.; Groshen, S.; Mehrian-Shai, R.; Delabie, J.; Chan, W. C.; Laird, P. W.; Hacia, J. G.

In: Leukemia, Vol. 22, No. 5, 01.01.2008, p. 1035-1043.

Research output: Contribution to journalArticle

Pike, BL, Greiner, TC, Wang, X, Weisenburger, DD, Hsu, YH, Renaud, G, Wolfsberg, TG, Kim, M, Weisenberger, DJ, Siegmund, KD, Ye, W, Groshen, S, Mehrian-Shai, R, Delabie, J, Chan, WC, Laird, PW & Hacia, JG 2008, 'DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status', Leukemia, vol. 22, no. 5, pp. 1035-1043. https://doi.org/10.1038/leu.2008.18
Pike, B. L. ; Greiner, Timothy Charles ; Wang, X. ; Weisenburger, D. D. ; Hsu, Y. H. ; Renaud, G. ; Wolfsberg, T. G. ; Kim, M. ; Weisenberger, D. J. ; Siegmund, K. D. ; Ye, W. ; Groshen, S. ; Mehrian-Shai, R. ; Delabie, J. ; Chan, W. C. ; Laird, P. W. ; Hacia, J. G. / DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status. In: Leukemia. 2008 ; Vol. 22, No. 5. pp. 1035-1043.
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