Epigenetic changes in the DAP-kinase CpG island in pediatric lymphoma

Med Pediatr Oncol. 2003 Dec;41(6):527-31. doi: 10.1002/mpo.10326.


Background: Hypermethylation of CpG islands in the promoter region of death-associated protein kinase (DAP-kinase) coupled with the loss of gamma-interferon-induced apoptosis have been reported in B-cell malignancies suggesting a role in pathogenesis or prognosis. Along with B-cell malignancies, pediatric lymphomas also include T-cell non-Hodgkin lymphoma (NHL), anaplastic large cell lymphoma, and Hodgkin disease, each with unique prognoses. The purpose of this study was to elucidate epigenetic changes in the DAP-kinase promoter region of pediatric cases to determine associations with aberrant hypermethylation.

Procedures: Thirty-nine cases of different lymphoid pathology [10 Burkitt lymphoma, 1 B-cell NHL; 7 T-cell lymphoblastic lymphoma; 4 anaplastic large cell lymphoma (LCL); 2 B-cell LCL; 14 nodular sclerosing Hodgkin disease (NSHD); and 1 B-cell acute lymphoblastic leukemia (ALL)] had methylation-specific polymerase chain reaction performed on bisulfite-treated DNA, which distinguishes the methylation status of the promoter region, and DAP-kinase mRNA expression assays performed on available specimens.

Results: In normal lymphocytes, the CpG islands in the promoter region were unmethylated, as were the T-cell lymphoblastic lymphoma and anaplastic LCL. In contrast, 100% of the Burkitt lymphoma (10/10) and B-cell ALL (1/1) were hypermethylated. Of the specimens with mRNA available, 7/8 Burkitt lymphoma had no DAP-kinase mRNA expression compared to normal expression in 3/3 and 4/4 T-cell lymphoblastic lymphoma and NSHD, respectively.

Conclusions: In these pediatric lymphoid tumors, hypermethylation of the DAP-kinase promoter region with associated loss of DAP-kinase gene expression was associated with B-cell malignancies and thus may be important in the development and/or provide a prognostic tool in B- cell lymphomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis Regulatory Proteins
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics*
  • Child
  • CpG Islands / genetics*
  • DNA Methylation*
  • DNA, Neoplasm / genetics*
  • Death-Associated Protein Kinases
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoma / genetics*
  • Male
  • Prognosis
  • Promoter Regions, Genetic / genetics


  • Apoptosis Regulatory Proteins
  • DNA, Neoplasm
  • Death-Associated Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases