PUBLICATION
Intronless WNT10B-short variant underlies new recurrent allele-specific rearrangement in acute myeloid leukaemia
- Authors
- Lazzaroni, F., Del Giacco, L., Biasci, D., Turrini, M., Prosperi, L., Brusamolino, R., Cairoli, R., Beghini, A.
- ID
- ZDB-PUB-180518-9
- Date
- 2016
- Source
- Scientific Reports 6: 37201 (Journal)
- Registered Authors
- Del Giacco, Luca, Prosperi, Laura
- Keywords
- none
- MeSH Terms
-
- Animals
- Female
- Gene Expression Regulation, Leukemic*
- Gene Rearrangement*
- Genetic Loci*
- Humans
- Introns*
- Leukemia, Myeloid, Acute*/genetics
- Leukemia, Myeloid, Acute*/metabolism
- Male
- Proto-Oncogene Proteins*/biosynthesis
- Proto-Oncogene Proteins*/genetics
- Wnt Proteins*/biosynthesis
- Wnt Proteins*/genetics
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics
- PubMed
- 27853307 Full text @ Sci. Rep.
Citation
Lazzaroni, F., Del Giacco, L., Biasci, D., Turrini, M., Prosperi, L., Brusamolino, R., Cairoli, R., Beghini, A. (2016) Intronless WNT10B-short variant underlies new recurrent allele-specific rearrangement in acute myeloid leukaemia. Scientific Reports. 6:37201.
Abstract
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 AC133bright leukaemia cells, although the existence of a specific mechanism remains unproven. We have obtained evidences for a recurrent rearrangement, which involved the WNT10B locus (WNT10BR) 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 (WNT10BIVS1) 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 WNT10BR. 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 WNT10BIVS1. 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.
Errata / Notes
This article is corrected by ZDB-PUB-220906-72.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping