Intronless WNT10B-short variant underlies new recurrent allele-specific rearrangement in acute myeloid leukaemia

• DOI: 10.1038/srep37201
• Publication Date: 2016-11-17T10:26:55Z
• Authors: Francesca Lazzaroni; Luca Del Giacco; Daniele Biasci; Mauro Turrini; Laura Prosperi; Roberto Brusamolino; Roberto Cairoli; Alessandro Beghini
• Keywords: Gene rearrangement

Abstract Defects in the control of Wnt signaling have emerged as a recurrent mechanism involved cancer pathogenesis and acute myeloid leukaemia (AML), including hematopoietic regeneration-associated WNT10B AC133 bright cells, although existence specific remains unproven. We obtained evidences for rearrangement, which locus (WNT10B R ) within intron 1 (IVS1) flanked at 5′ by non-human sequences whose origin to be elucidated; it also expressed transcript variant IVS1 was mainly detected cohort patients with intermediate/unfavorable risk AML. identified two separate cases, affected AML breast respectively, genomic transposable short form human (ht-WNT10B). The intronless ht-WNT10B resembles long non-coding RNA (lncRNA), suggests its involvement non-random microhomology-mediated recombination generating rearranged . Furthermore, our studies supports an autocrine activation primed formation WNT10B-FZD4/5 complexes MCF7 cells that express Chemical interference WNT-ligands production porcupine inhibitor IWP-2 achieved dose-dependent suppression interactions. These results present first evidence rearrangement promoted mobile oncogene, relevant cancer.