Article (Scientific journals)
Cis-perturbation of cancer drivers by the HTLV-1/BLV proviruses is an early determinant of leukemogenesis
Rosewick, Nicolas; Durkin, Keith; Artesi, Maria et al.
2017In Nature Communications, 8
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Keywords :
Retrovirus; cancer; leukemia; HTLV; BLV; genomic; RNA sequencing; Tumor virus infections
Research center :
Giga-Genetics - ULiège
Disciplines :
Genetics & genetic processes
Author, co-author :
Rosewick, Nicolas ;  Institut Jules Bordet, Université Libre de Bruxelles (ULB) > Laboratory of Experimental Hematology
Durkin, Keith   ;  Université de Liège > Département des productions animales (DPA) > GIGA-R : Génomique animale
Artesi, Maria  ;  Université de Liège > GIGA-Research
Marçais, Ambroise;  Hôpital Universitaire Necker, Université René Descartes > Service d’hématologie
Hahaut, Vincent ;  Université de Liège > Département des productions animales (DPA) > GIGA-R : Génomique animale
Griebel, Philip;  VIDO-Intervac, University of Saskatchewan > Vaccine and Infectious Disease Organization
Avettand-Fenoel, Véronique;  AP-HP, Hôpital Necker-Enfants Malades, Université Paris Descartes > Laboratoire de Virologie
Burny, Arsène ;  Université de Liège - ULiège > Agro Biotech Gembloux
Charlier, Carole  ;  Université de Liège > Département des productions animales (DPA) > GIGA-R : Génomique animale
Hermine, Olivier;  Hôpital Universitaire Necker, Université René Descartes > Service d’hématologie
Georges, Michel  ;  Université de Liège > Département des productions animales (DPA) > GIGA-R : Génomique animale
Van den Broeke, Anne;  Institut Jules Bordet, Université Libre de Bruxelles (ULB) > Laboratory of Experimental Hematology
 These authors have contributed equally to this work.
Language :
English
Title :
Cis-perturbation of cancer drivers by the HTLV-1/BLV proviruses is an early determinant of leukemogenesis
Publication date :
23 May 2017
Journal title :
Nature Communications
eISSN :
2041-1723
Publisher :
Nature Pub.lishing Group, London, United Kingdom
Volume :
8
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Télévie [BE]
Les amis de l'institut Bordet
International Brachet Stiftung (IBS)
Fondation Lambeau-Marteaux
Ligue contre le cancer
INCa - Institut National du Cancer [FR]
Cancéropôle Ile-de-France [FR]
Commentary :
Human T-cell leukaemia virus type-1 (HTLV-1) and bovine leukaemia virus (BLV) infect T- and B-lymphocytes, respectively, provoking a polyclonal expansion that will evolve into an aggressive monoclonal leukaemia in ∼5% of individuals following a protracted latency period. It is generally assumed that early oncogenic changes are largely dependent on virus-encoded products, especially TAX and HBZ, while progression to acute leukaemia/lymphoma involves somatic mutations, yet that both are independent of proviral integration site that has been found to be very variable between tumours. Here, we show that HTLV-1/BLV proviruses are integrated near cancer drivers which they affect either by provirus-dependent transcription termination or as a result of viral antisense RNA-dependent cis-perturbation. The same pattern is observed at polyclonal non-malignant stages, indicating that provirus-dependent host gene perturbation contributes to the initial selection of the multiple clones characterizing the asymptomatic stage, requiring additional alterations in the clone that will evolve into full-blown leukaemia/lymphoma.
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since 27 June 2017

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