Journal
NATURE COMMUNICATIONS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms4904
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Funding
- Damon Runyon Cancer Research Foundation
- Lymphoma Research Foundation
- Gabrielle's Angel Foundation for Cancer Research
- Leukemia and Lymphoma Society
- National Institutes of Health
- Department of Defense
- FEDER
- MICINN [SAF2009-08803, SAF2012-32810]
- Junta de Castilla y Leon [CSI13A08, GR15, SA060A09]
- MEC OncoBIO Consolider-Ingenio [CSD2007-0017]
- National Institutes of Health (NIH) [R01 CA10933504A1]
- NIH [U01HL099999]
- NCI [R01 CA104348]
- Chemotherapy Foundation
- Sam Waxman Cancer Research Foundation
- GP Foundation
- Leukemia and Lymphoma Society Scholar
- Fondo de Investigaciones Sanitarias [PI080164]
- Proyectos Intramurales Especiales (CSIC)
- Instituto de Salud Carlos III
- Ministerio de Sanidad y Consumo, Madrid, Spain [IISCIII-RTICC RD06/0020/0035-FEDER]
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Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma and can be separated into two subtypes based upon molecular features with similarities to germinal centre B-cells (GCB-like) or activated B-cells (ABC-like). Here we identify gain of 3q27.2 as being significantly associated with adverse outcome in DLBCL and linked with the ABC-like subtype. This lesion includes the BCL6 oncogene, but does not alter BCL6 transcript levels or target-gene repression. Separately, we identify expression of BCL6 in a subset of human haematopoietic stem/progenitor cells (HSPCs). We therefore hypothesize that BCL6 may act by 'hit-and-run' oncogenesis. We model this hit-and-run mechanism by transiently expressing Bcl6 within murine HSPCs, and find that it causes mature B-cell lymphomas that lack Bcl6 expression and target-gene repression, are transcriptionally similar to post-GCB cells, and show epigenetic changes that are conserved from HSPCs to mature B-cells. Together, these results suggest that BCL6 may function in a 'hit-and-run' role in lymphomagenesis.
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