Details

Autor(en) / Beteiligte

• Rosewick, Nicolas
• Durkin, Keith
• Artesi, Maria
• Marçais, Ambroise
• Hahaut, Vincent
• Griebel, Philip
• Arsic, Natasa
• Avettand-Fenoel, Véronique
• Burny, Arsène
• Charlier, Carole
• Hermine, Olivier
• Georges, Michel
• Van den Broeke, Anne

Titel

Cis-perturbation of cancer drivers by the HTLV-1/BLV proviruses is an early determinant of leukemogenesis

Ist Teil von

• Nature communications, 2017-05, Vol.8 (1), p.15264-15264, Article 15264

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.