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

作者：Lamprecht Bjoern; Walter Korden; Kreher Stephan; Kumar Raman; Hummel Michael; Lenze Dido; Koechert Karl; Bouhlel Mohamed Amine; Richter Julia; Soler Eric; Stadhouders Ralph; Joehrens Korinna; Wurster Kathrin D; Callen David F; Harte Michael F; Giefing Maciej; Barlow Rachael; Stein Harald; Anagnostopoulos Ioannis; Janz Martin; Cockerill Peter N; Siebert Reiner; Doerken Bernd; Bonifer Constanze; Mathas Stephan^*

来源：Nature Medicine, 2010, 16(5): 571-579.

DOI：10.1038/nm.2129

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.

• 出版日期2010-5