• DOI:10.1182/blood-2011-12-401471
• Corpus ID: 14638050

Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing.

@article{Dolnik2012CommonlyAG,
  title={Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing.},
  author={Anna Dolnik and Julia C. Engelmann and Maren Scharfenberger-Schmeer and Julian Mauch and Sabine Kelkenberg-Schade and Berit Haldemann and Tamara Fries and Jan Kr{\"o}nke and Michael W. M. K{\"u}hn and Peter Paschka and Sabine Kayser and Stephan E. Wolf and Verena Gaidzik and Richard F. Schlenk and Frank G. R{\"u}cker and Hartmut D{\"o}hner and Claudio Lottaz and Konstanze D{\"o}hner and Lars Bullinger},
  journal={Blood},
  year={2012},
  volume={120 18},
  pages={
          e83-92
        }
}

• A. Dolnik, J. Engelmann, +16 authors L. Bullinger
• Published 1 November 2012
• Biology
• Blood

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.