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

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

doi:10.1038/nm.2129

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

Björn Lamprecht, Korden Walter, Stephan Kreher, Raman Kumar, Michael Hummel, Dido Lenze, Karl Köchert, Mohamed Amine Bouhlel, Julia Richter, Eric Soler, Ralph Stadhouders, Korinna Jöhrens, Kathrin D Wurster, David F Callen, Michael F Harte, Maciej Giefing, Rachael Barlow, Harald Stein, Ioannis Anagnostopoulos, Martin JanzPeter N Cockerill, Reiner Siebert, Bernd Dörken, Constanze Bonifer, Stephan Mathas

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216 Citations (Scopus)

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.

Original language	English
Pages (from-to)	571-9, 1p following 579
Journal	Nature Medicine
Volume	16
Issue number	5
DOIs	https://doi.org/10.1038/nm.2129
Publication status	Published - 1 May 2010

Keywords

CSF1R
proto-oncogene

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1038/nm.2129

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Lamprecht, B., Walter, K., Kreher, S., Kumar, R., Hummel, M., Lenze, D., Köchert, K., Bouhlel, M. A., Richter, J., Soler, E., Stadhouders, R., Jöhrens, K., Wurster, K. D., Callen, D. F., Harte, M. F., Giefing, M., Barlow, R., Stein, H., Anagnostopoulos, I., ... Mathas, S. (2010). Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma. Nature Medicine, 16(5), 571-9, 1p following 579. https://doi.org/10.1038/nm.2129

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

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 = "CSF1R, proto-oncogene",

author = "Bj{\"o}rn Lamprecht and Korden Walter and Stephan Kreher and Raman Kumar and Michael Hummel and Dido Lenze and Karl K{\"o}chert and Bouhlel, {Mohamed Amine} and Julia Richter and Eric Soler and Ralph Stadhouders and Korinna J{\"o}hrens and Wurster, {Kathrin D} and Callen, {David F} and Harte, {Michael F} and Maciej Giefing and Rachael Barlow and Harald Stein and Ioannis Anagnostopoulos and Martin Janz and Cockerill, {Peter N} and Reiner Siebert and Bernd D{\"o}rken and Constanze Bonifer and Stephan Mathas",

year = "2010",

month = may,

day = "1",

doi = "10.1038/nm.2129",

language = "English",

volume = "16",

pages = "571--9, 1p following 579",

journal = "Nature Medicine",

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Lamprecht, B, Walter, K, Kreher, S, Kumar, R, Hummel, M, Lenze, D, Köchert, K, Bouhlel, MA, Richter, J, Soler, E, Stadhouders, R, Jöhrens, K, Wurster, KD, Callen, DF, Harte, MF, Giefing, M, Barlow, R, Stein, H, Anagnostopoulos, I, Janz, M, Cockerill, PN, Siebert, R, Dörken, B, Bonifer, C & Mathas, S 2010, 'Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma', Nature Medicine, vol. 16, no. 5, pp. 571-9, 1p following 579. https://doi.org/10.1038/nm.2129

TY - JOUR

T1 - Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma

AU - Lamprecht, Björn

AU - Walter, Korden

AU - Kreher, Stephan

AU - Kumar, Raman

AU - Hummel, Michael

AU - Lenze, Dido

AU - Köchert, Karl

AU - Bouhlel, Mohamed Amine

AU - Richter, Julia

AU - Soler, Eric

AU - Stadhouders, Ralph

AU - Jöhrens, Korinna

AU - Wurster, Kathrin D

AU - Callen, David F

AU - Harte, Michael F

AU - Giefing, Maciej

AU - Barlow, Rachael

AU - Stein, Harald

AU - Anagnostopoulos, Ioannis

AU - Janz, Martin

AU - Cockerill, Peter N

AU - Siebert, Reiner

AU - Dörken, Bernd

AU - Bonifer, Constanze

AU - Mathas, Stephan

PY - 2010/5/1

Y1 - 2010/5/1

N2 - 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.

AB - 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.

KW - CSF1R

KW - proto-oncogene

U2 - 10.1038/nm.2129

DO - 10.1038/nm.2129

M3 - Article

C2 - 20436485

SN - 1546-170X

VL - 16

SP - 571-9, 1p following 579

JO - Nature Medicine

JF - Nature Medicine

IS - 5

ER -

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

Abstract

Keywords

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