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Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma

Item Type:Article
Title:Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma
Creators Name:Lamprecht, B., Walter, K., Kreher, S., Kumar, R., Hummel, M., Lenze, D., Koechert, K., Bouhlel, M.A., Richter, J., Soler, E., Stadhouders, R., Joehrens, K., Wurster, K.D., Callen, D.F., Harte, M.F., Giefing, M., Barlow, R., Stein, H., Anagnostopoulos, I., Janz, M., Cockerill, P.N., Siebert, R., Doerken, B., Bonifer, C. and Mathas, S.
Abstract:Mammalian genomes contain many repetitive elements, including long terminal repeats (LTRs), which have long been suspected to have a role in tumorigenesis. Here we present evidence that aberrant LTR activation contributes to lineage-inappropriate gene expression in transformed human cells and that such gene expression is central for tumor cell survival. We show that B cell-derived Hodgkin's lymphoma cells depend on the activity of the non-B, myeloid-specific proto-oncogene colony-stimulating factor 1 receptor (CSF1R). In these cells, CSF1R transcription initiates at an aberrantly activated endogenous LTR of the MaLR family (THE1B). Derepression of the THE1 subfamily of MaLR LTRs is widespread in the genome of Hodgkin's lymphoma cells and is associated with impaired epigenetic control due to loss of expression of the corepressor CBFA2T3. Furthermore, we detect LTR-driven CSF1R transcripts in anaplastic large cell lymphoma, in which CSF1R is known to be expressed aberrantly. We conclude that LTR derepression is involved in the pathogenesis of human lymphomas, a finding that might have diagnostic, prognostic and therapeutic implications.
Keywords:Colony-Stimulating Factors, Gene Expression, Hodgkin Disease, Lymphoma, B-Cell Lymphoma, Macrophage Colony-Stimulating Factor, Phosphoproteins, Proto-Oncogenes, Repressor Proteins, Terminal Repeat Sequences, Tumor Suppressor Proteins
Source:Nature Medicine
Publisher:Nature Publishing Group
Page Range:571-579, 1p following 579
Date:May 2010
Official Publication:https://doi.org/10.1038/nm.2129
PubMed:View item in PubMed

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