title: Large-scale analysis of DNA methylation in chronic lymphocytic leukemia.
abstract: OBJECTIVE
  B-cell chronic lymphocytic leukemia (CLL) is a heterogeneous malignancy that clinically ranges from indolent to rapidly progressive. CLL, like other cancers, can be affected by epigenetic alterations.
  
  
  METHODS
  A microarray discovery-based study was initiated to determine DNA methylation in CLL cases with a range of CD38 expression (1–92%).
  
  
  RESULTS
  Many loci were either methylated or unmethylated across all CD38 levels, but differential methylation was also observed for some genes. Genomic sequencing of DLEU7 confirmed extensive cytosine methylation preferentially in patient samples with low CD38 expression, whereas NRP2, SFRP2 and ADAM12 were more commonly methylated in those with high CD38 expression.
  
  
  CONCLUSIONS
  This study demonstrates that CLL is affected by CpG island methylation in some genes that segregate with CD38 expression levels, while most others show similar methylation patterns across all levels. The CpG island methylation in certain functional gene groups and pathway-associated genes that are known to be deregulated in CLL provides additional insights into the CLL methylome and epigenetic contribution to cellular dysfunction. It will now be useful to investigate the effectiveness of epigenetic therapeutic reversal of these alterations to develop effective treatments for the disease.
authors.affiliation: Department of Pathology and Anatomical Sciences, Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, Missouri 65212, USA.
authors.forename: Farahnaz B
authors.initials: FB
authors.lastname: Rahmatpanah
authors.forename: Stephanie
authors.initials: S
authors.lastname: Carstens
authors.forename: Sam I
authors.initials: SI
authors.lastname: Hooshmand
authors.forename: Elise C
authors.initials: EC
authors.lastname: Welsh
authors.forename: Ozy
authors.initials: O
authors.lastname: Sjahputera
authors.forename: Kristen H
authors.initials: KH
authors.lastname: Taylor
authors.forename: Lynda B
authors.initials: LB
authors.lastname: Bennett
authors.forename: Huidong
authors.initials: H
authors.lastname: Shi
authors.forename: J Wade
authors.initials: JW
authors.lastname: Davis
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Arthur
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.forename: James E
authors.initials: JE
authors.lastname: Wooldridge
authors.forename: Charles W
authors.initials: CW
authors.lastname: Caldwell
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000072199:ADAM12 Protein; D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018899:CpG Islands; D004247:DNA / Q000032:analysis*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D056426:Genetic Loci; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D051722:ADAM Proteins; D000072199:ADAM12 Protein; D051997:ADP-ribosyl Cyclase 1; D004247:DNA; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D039943:Neuropilin-2; D025521:Tumor Suppressor Proteins; C482307:DLEU7 protein, human; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C000606480:ADAM12 protein, human