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

نویسندگان

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

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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عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2017