Large-scale analysis of DNA methylation in chronic lymphocytic leukemia. Epigenomics 2009 Oct;1(1):39-61
Date
05/25/2010Pubmed ID
20495622Pubmed Central ID
PMC2872502DOI
10.2217/epi.09.10Scopus ID
2-s2.0-77954126563 (requires institutional sign-in at Scopus site) 48 CitationsAbstract
AIMS: 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.
MATERIALS & 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.
CONCLUSION: 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.
Author List
Rahmatpanah FB, Carstens S, Hooshmand SI, Welsh EC, Sjahputera O, Taylor KH, Bennett LB, Shi H, Davis JW, Arthur GL, Shanafelt TD, Kay NE, Wooldridge JE, Caldwell CWAuthor
Sam I. Hooshmand DO Assistant Professor in the Neurology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ADAM ProteinsADAM12 Protein
ADP-ribosyl Cyclase 1
Cell Line, Tumor
Cluster Analysis
CpG Islands
DNA
DNA Methylation
Epigenesis, Genetic
Genetic Loci
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
Membrane Proteins
Middle Aged
Neoplasm Proteins
Neuropilin-2
Oligonucleotide Array Sequence Analysis
Sequence Analysis, DNA
Tumor Suppressor Proteins
