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  Altered DNA Methylation Profiles in SF3B1 Mutated CLL Patients

Pacholewska, A., Grimm, C., Herling, C. D., Lienhard, M., Königs, A., Timmermann, B., et al. (2021). Altered DNA Methylation Profiles in SF3B1 Mutated CLL Patients. International Journal of Molecular Sciences, 22(17): 9337. doi:10.3390/ijms22179337.

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Pacholewska, Alicja , Author
Grimm, Christina , Author
Herling, Carmen D. , Author
Lienhard, Matthias1, Author           
Königs, Anja, Author
Timmermann, Bernd2, Author           
Altmüller, Janine , Author
Mücke, Oliver, Author
Reinhardt, Hans Christian , Author
Plass, Christoph, Author
Herwig, Ralf1, Author           
Hallek, Michael , Author
Schweiger, Michal R. , Author
Affiliations:
1Bioinformatics (Ralf Herwig), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385701              
2Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

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Free keywords: chronic lymphocytic leukemia; CLL; DNA methylation; SF3B1 mutation; NOTCH; IKAROS
 Abstract: Mutations in splicing factor genes have a severe impact on the survival of cancer patients. Splicing factor 3b subunit 1 (SF3B1) is one of the most frequently mutated genes in chronic lymphocytic leukemia (CLL); patients carrying these mutations have a poor prognosis. Since the splicing machinery and the epigenome are closely interconnected, we investigated whether these alterations may affect the epigenomes of CLL patients. While an overall hypomethylation during CLL carcinogenesis has been observed, the interplay between the epigenetic stage of the originating B cells and SF3B1 mutations, and the subsequent effect of the mutations on methylation alterations in CLL, have not been investigated. We profiled the genome-wide DNA methylation patterns of 27 CLL patients with and without SF3B1 mutations and identified local decreases in methylation levels in SF3B1mut CLL patients at 67 genomic regions, mostly in proximity to telomeric regions. These differentially methylated regions (DMRs) were enriched in gene bodies of cancer-related signaling genes, e.g., NOTCH1, HTRA3, and BCL9L. In our study, SF3B1 mutations exclusively emerged in two out of three epigenetic stages of the originating B cells. However, not all the DMRs could be associated with the methylation programming of B cells during development, suggesting that mutations in SF3B1 cause additional epigenetic aberrations during carcinogenesis.

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Language(s): eng - English
 Dates: 2021-08-252021-08-28
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.3390/ijms22179337
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Title: International Journal of Molecular Sciences
  Abbreviation : Int. J. Mol. Sci.
Source Genre: Journal
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Publ. Info: Basel, Switzerland : MDPI AG
Pages: - Volume / Issue: 22 (17) Sequence Number: 9337 Start / End Page: - Identifier: ISSN: 1422-0067
CoNE: https://pure.mpg.de/cone/journals/resource/1422-0067