Epigenetic profile in chronic lymphocytic leukemia using methylation-specific multiplex ligation-dependent probe amplification

Epigenomics. 2012 Oct;4(5):491-501. doi: 10.2217/epi.12.40.

Abstract

Aim: To analyze the methylation status of 35 tumor suppressor genes using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in chronic lymphocytic leukemia (CLL).

Materials & methods: The DNA of 37 samples from patients with CLL, six healthy donors, and Jurkat and Ramos cell lines was analyzed by MS-MLPA.

Results: Our results confirm that hypermethylation is a common and not randomly distributed event in CLL, and some genes, such as WT1, CDH13, IGSF4/TSLC1, GATA5, DAPK1 and RARB, are hypermethylated in more than 25% of the analyzed samples. Importantly, MS-MLPA also detected hypermethylation of some genes not reported previously in CLL, and their methylation status was confirmed by bisulfite sequencing.

Conclusion: These results indicate that MS-MLPA is a useful technique for the detection of methylation in CLL samples. Selecting CLL-specific methylation targets in order to generate a CLL-specific MS-MLPA probe set could enhance its usefulness as a tool in studies of risk stratification and guiding the best therapeutic decision.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cadherins / genetics
  • Case-Control Studies
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Female
  • Genes, Tumor Suppressor*
  • Genes, Wilms Tumor
  • Genetic Variation
  • Humans
  • Jurkat Cells
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Multiplex Polymerase Chain Reaction / methods*
  • Promoter Regions, Genetic
  • Receptors, Retinoic Acid / genetics
  • Reproducibility of Results

Substances

  • Cadherins
  • H-cadherin
  • Receptors, Retinoic Acid
  • retinoic acid receptor beta