Dolnik, Anna and Engelmann, Julia C. and Scharfenberger-Schmeer, Maren and Mauch, Julian and Kelkenberg-Schade, Sabine and Haldemann, Berit and Fries, Tamara and Kroenke, Jan and Kuehn, Michael W. M. and Paschka, Peter and Kayser, Sabine and Wolf, Stephan and Gaidzik, Verena I. and Schlenk, Richard F. and Ruecker, Frank G. and Doehner, Hartmut and Lottaz, Claudio and Doehner, Konstanze and Bullinger, Lars (2012) Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing. BLOOD, 120 (18). E83-E92. ISSN 0006-4971,
Full text not available from this repository. (Request a copy)Abstract
Acute myeloid leukemia (AML) is characterized by molecular heterogeneity. As commonly altered genomic regions point to candidate genes involved in leukemogenesis, we used microarray-based comparative genomic hybridization and single nucleotide polymorphism profiling data of 391 AML cases to further narrow down genomic regions of interest. Targeted re-sequencing of 1000 genes located in the critical regions was performed in a representative cohort of 50 AML samples comprising all major cytogenetic subgroups. We identified 120 missense/nonsense mutations as well as 60 insertions/deletions affecting 73 different genes (similar to 3.6 tumor-specific aberrations/AML). While most of the newly identified alterations were non-recurrent, we observed an enrichment of mutations affecting genes involved in epigenetic regulation including known candidates like TET2, TET1, DNMT3A, and DNMT1, as well as mutations in the histone methyltransferases NSD1, EZH2, and MLL3. Furthermore, we found mutations in the splicing factor SFPQ and in the nonclassic regulators of mRNA processing CTCF and RAD21. These splicing-related mutations affected 10% of AML patients in a mutually exclusive manner. In conclusion, we could identify a large number of alterations in genes involved in aberrant splicing and epigenetic regulation in genomic regions commonly altered in AML, highlighting their important role in the molecular pathogenesis of AML. (Blood. 2012;120(18):e83-e92)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACUTE LYMPHOBLASTIC-LEUKEMIA; GENETIC ALTERATIONS; IDH2 MUTATIONS; CELL CARCINOMA; TET2; PSF; MYELODYSPLASIA; TRANSCRIPTION; EXPRESSION; LYMPHOMA; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 May 2020 04:50 |
| Last Modified: | 05 May 2020 04:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17846 |
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