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  • 标题:Intronless WNT10B-short variant underlies new recurrent allele-specific rearrangement in acute myeloid leukaemia
  • 本地全文:下载
  • 作者:Francesca Lazzaroni ; Luca Del Giacco ; Daniele Biasci
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2016
  • 卷号:6
  • 期号:1
  • DOI:10.1038/srep37201
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:Defects in the control of Wnt signaling have emerged as a recurrent mechanism involved in cancer pathogenesis and acute myeloid leukaemia (AML), including the hematopoietic regeneration-associated WNT10B in AC133(bright) leukaemia cells, although the existence of a specific mechanism remains unproven. We have obtained evidences for a recurrent rearrangement, which involved the WNT10B locus (WNT10B(R)) within intron 1 (IVS1) and flanked at the 5' by non-human sequences whose origin remains to be elucidated; it also expressed a transcript variant (WNT10B(IVS1)) which was mainly detected in a cohort of patients with intermediate/unfavorable risk AML. We also identified in two separate cases, affected by AML and breast cancer respectively, a genomic transposable short form of human WNT10B (ht-WNT10B). The intronless ht-WNT10B resembles a long non-coding RNA (lncRNA), which suggests its involvement in a non-random microhomology-mediated recombination generating the rearranged WNT10B(R). Furthermore, our studies supports an autocrine activation primed by the formation of WNT10B-FZD4/5 complexes in the breast cancer MCF7 cells that express the WNT10B(IVS1). Chemical interference of WNT-ligands production by the porcupine inhibitor IWP-2 achieved a dose-dependent suppression of the WNT10B-FZD4/5 interactions. These results present the first evidence for a recurrent rearrangement promoted by a mobile ht-WNT10B oncogene, as a relevant mechanism for Wnt involvement in human cancer.
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