CpG island methylation patterns in chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. In CLL, a large number of genes affecting cancer-related pathways may be dysregulated by epigenetic silencing. We analysed by methylation-specific polymerase chain reaction the CpG island methylation status of 15 well-characterised cancer-related genes in 32 patients with CLL. Aberrant methylation in the sample of patients with CLL was shown for secreted frizzled-related protein 1 (68.8%), secreted frizzled-related protein 2 (65.6%), death-associated protein kinase 1 (50.0%), E-cadherin (21.9%), secreted frizzled-related protein 4 (15.6%), p15 (9.4%), p16 (6.3%), retinoic acid receptor beta2 (3.1%), secreted frizzled-related protein 5 (3.1%) and tissue inhibitor of matrix metalloproteinases 3 (3.1%). For human Mut-L homolog 1, O(6)-methylguanine DNA methyltransferase, p73, suppressor of cytokine signalling 1 and tissue inhibitor of matrix metalloproteinases 2 no hypermethylation was detected. Hypermethylation of at least one gene was observed in 87.5% of the samples. Our results show that aberrant CpG island methylation affecting cancer-related pathways such as Wnt signalling, regulation of apoptosis, cell cycle control and tissue invasion is a common phenomenon in CLL. Epigenetic disturbances may be involved in the pathogenesis of CLL and thus may provide a molecular rationale for therapeutic approaches.
Medizinische Klinik IV, Universitaetsklinikum Aachen, RWTH Aachen, Aachen, Germany.
Barbara
B
Seeliger
Stefan
S
Wilop
Rainhardt
R
Osieka
Oliver
O
Galm
Edgar
E
Jost
D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D016133:Polymerase Chain Reaction; D051153:Wnt Proteins / Q000235:genetics
D051153:Wnt Proteins