| Item type: | Article | ||||||||||||||||||
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| Journal or Publication Title: | Blood | ||||||||||||||||||
| Publisher: | American Society of Hematology | ||||||||||||||||||
| Volume: | 120 | ||||||||||||||||||
| Number of Issue or Book Chapter: | 18 | ||||||||||||||||||
| Page Range: | e83-e92 | ||||||||||||||||||
| Date: | 1 November 2012 | ||||||||||||||||||
| Institutions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) Informatics and Data Science > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) | ||||||||||||||||||
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| Classification: |
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| Keywords: | Chromatin Assembly and Disassembly, genetics; Comparative Genomic Hybridization; Humans; Leukemia, Myeloid, Acute, genetics; Mutation; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; RNA Splicing, genetics | ||||||||||||||||||
| Dewey Decimal Classification: | 500 Science > 500 Natural sciences & mathematics 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine | ||||||||||||||||||
| Status: | Published | ||||||||||||||||||
| Refereed: | Yes, this version has been refereed | ||||||||||||||||||
| Created at the University of Regensburg: | Partially | ||||||||||||||||||
| Item ID: | 30595 |
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 resequencing of 1000 genes located in the ...
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 resequencing 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 (∼ 3.6 tumor-specific aberrations/AML). While most of the newly identified alterations were nonrecurrent, 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.
Metadata last modified: 29 Sep 2021 07:40
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