Identification of mitochondrial genome concatemers in AIDS-associated lymphomas and lymphoid cell lines

Felipe Bedoya, Maria M. Medveczky, Troy C. Lund, Andras Perl, Joseph Horvath, Stephen D. Jett, Peter G. Medveczky

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Since most oncogenic viruses persist as extrachromosomal covalently closed circular DNA (cccDNA) in tumor cells, we developed an assay to visualize and identify cccDNA in primary lymphomas. We identified concatemers of the mitochondrial genome in all samples analyzed, but not in normal lymphocytes. One AIDS-associated lymphoma (EL) was further studied in detail as its mitochondrial genome consisted of tandem head-to-tail duplications. Insertion of C-residues was noted near the origin of replication of EL mtDNA. EL cells responded weakly to Fas-apoptotic stimulus, displayed reduced mitochondrial activity and mass, and produced higher levels of reactive oxygen intermediates. Screening of several AIDS-associated lymphomas and established lymphoid cell lines also revealed the presence of mitochondrial genome concatemers consisting of interlinked monomer molecules. Taken together, our results suggest that formation of mtDNA concatemers is associated with oncogenic transformation in lymphoid cells.

Original languageEnglish (US)
Pages (from-to)1499-1504
Number of pages6
JournalLeukemia research
Volume33
Issue number11
DOIs
StatePublished - Nov 2009

Bibliographical note

Funding Information:
We thank Shara Pantry for helpful suggestions on this manuscript. This work was supported by NIH grant RO1CA111196 to P.M.

Keywords

  • AIDS-associated lymphomas
  • Leukemogenesis
  • Mitochondria
  • Mitochondrial DNA concatemers
  • Oncogenic transformation

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