Selective variegated methylation of the p15 CpG island in acute myeloid leukemia

Jonathan E. Dodge, Alan F. List, Bernard W. Futscher

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Both p15 and p16 are tumor suppressor genes that have 5' CpG islands; aberrant cytosine methylation of these islands has been associated with silencing of their expression. Deoxycytidine kinase (dCK) converts prodrugs to their cytotoxic form, has a 5' CpG island and is a candidate gene for inactivation by hypermethylation. In our study, we used sodium bisulfite sequencing to generate high resolution maps of 5-methylcytosine in the CpG islands associated with p15, p16 and dCK in normal human bone marrow (BM), peripheral blood lymphocytes (PBL) and cytosine arabinoside (ara-C)-resistant acute myeloid leukemia (AML) patients, and established human hematopoietic tumor cell lines. In normal cells the p15, p16 and dCK CpG islands were largely unmethylated. The p16 and dCK CpG islands were also unmethylated in the 8 AML specimens. In contrast, the p15 CpG island was aberrantly methylated in 6 of the 8 AML specimens. Furthermore, bisulfite sequencing revealed that the p15 CpG island is heterogeneously methylated in AML, with large intra-individual and inter-individual variability.

Original languageEnglish (US)
Pages (from-to)561-567
Number of pages7
JournalInternational Journal of Cancer
Volume78
Issue number5
DOIs
StatePublished - 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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