MYC-containing amplicons in acute myeloid leukemia: Genomic structures, evolution, and transcriptional consequences.

Details

Serval ID
serval:BIB_83964097FC5A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
MYC-containing amplicons in acute myeloid leukemia: Genomic structures, evolution, and transcriptional consequences.
Journal
Leukemia
Author(s)
ĹAbbate A., Tolomeo D., Cifola I., Severgnini M., Turchiano A., Augello B., Squeo G., D Addabbo P., Traversa D., Daniele G., Lonoce A., Pafundi M., Carella M., Palumbo O., Dolnik A., Muehlematter D., Schoumans J., Van Roy N., De Bellis G., Martinelli G., Merla G., Bullinger L., Haferlach C., Storlazzi C.T.
ISSN
1476-5551 (Electronic)
ISSN-L
0887-6924
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Double minutes (dmin), homogeneously staining regions, and ring chromosomes are vehicles of gene amplification in cancer. The underlying mechanism leading to their formation as well as their structure and function in acute myeloid leukemia (AML) remain mysterious. We combined a range of high-resolution genomic methods to investigate the architecture and expression pattern of amplicons involving chromosome band 8q24 in 23 cases of AML (AML-amp). This revealed that different MYC-dmin architectures can coexist within the same leukemic cell population, indicating a step-wise evolution rather than a single event origin, such as through chromothripsis. This was supported also by the analysis of the chromothripsis criteria, that poorly matched the model in our samples. Furthermore, we found that dmin could evolve toward ring chromosomes stabilized by neocentromeres. Surprisingly, amplified genes (mainly PVT1) frequently participated in fusion transcripts lacking a corresponding DNA template. We also detected a significant overexpression of the circular RNA of PVT1 (circPVT1) in AML-amp cases versus AML with a normal karyotype. Our results show that 8q24 amplicons in AML are surprisingly plastic DNA structures with an unexpected association to novel fusion transcripts and circular RNAs.Leukemia accepted article preview online, 28 November 2017. doi:10.1038/leu.2017.337.

Pubmed
Open Access
Yes
Create date
30/11/2017 19:30
Last modification date
19/12/2019 21:23
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