2. Academic Validation
  3. Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms

Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms

  • Cancer Cell. 2015 May 11;27(5):658-70. doi: 10.1016/j.ccell.2015.03.017.
Chantana Polprasert 1,  Isabell Schulze 2,  Mikkael A Sekeres 3,  Hideki Makishima 4,  Bartlomiej Przychodzen 4,  Naoko Hosono 5,  Jarnail Singh 6,  Richard A Padgett 6,  Xiaorong Gu 4,  James G Phillips 4,  Michael Clemente 4,  Yvonne Parker 4,  Daniel Lindner 4,  Brittney Dienes 4,  Eckhard Jankowsky 7,  Yogen Saunthararajah 4,  Yang Du 8,  Kevin Oakley 8,  Nhu Nguyen 8,  Sudipto Mukherjee 9,  Caroline Pabst 10,  Lucy A Godley 11,  Jane E Churpek 11,  Daniel A Pollyea 12,  Utz Krug 13,  Wolfgang E Berdel 13,  Hans-Ulrich Klein 14,  Martin Dugas 14,  Yuichi Shiraishi 15,  Kenichi Chiba 15,  Hiroko Tanaka 15,  Satoru Miyano 15,  Kenichi Yoshida 16,  Seishi Ogawa 16,  Carsten Müller-Tidow 17,  Jaroslaw P Maciejewski 18
Affiliations

Affiliations

  • 1 Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland, OH 44195, USA; Department of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
  • 2 Department of Hematology and Oncology, University of Halle, Halle 06108, Germany; Department of Hematology and Oncology, University of Muenster, Muenster 48149, Germany.
  • 3 Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland, OH 44195, USA; Leukemia Program, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH 44195, USA.
  • 4 Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland, OH 44195, USA.
  • 5 Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland, OH 44195, USA; First Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-8507, Japan.
  • 6 Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
  • 7 Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA.
  • 8 Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
  • 9 Leukemia Program, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH 44195, USA.
  • 10 Department of Hematology and Oncology, University of Halle, Halle 06108, Germany.
  • 11 Department of Medicine, Comprehensive Cancer Center and Center for Clinical Cancer Genetics, University of Chicago, Chicago, IL 60637, USA.
  • 12 University of Colorado School of Medicine and University of Colorado Cancer Center, Aurora, CO 80045, USA.
  • 13 Department of Hematology and Oncology, University of Muenster, Muenster 48149, Germany.
  • 14 Institute of Medical Informatics, University of Muenster, Muenster 48149, Germany.
  • 15 Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 113-8654, Japan.
  • 16 Department of Pathology and Tumor Biology, Kyoto University, Kyoto 606-8501, Japan.
  • 17 Department of Hematology and Oncology, University of Halle, Halle 06108, Germany; Department of Hematology and Oncology, University of Muenster, Muenster 48149, Germany. Electronic address: carsten.mueller-tidow@uk-halle.de.
  • 18 Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland, OH 44195, USA; Leukemia Program, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH 44195, USA. Electronic address: maciejj@ccf.org.
PMID: 25920683 DOI: 10.1016/j.ccell.2015.03.017
Abstract

Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. Moreover, corresponding deletions on 5q35.3 present in 6% of cases led to haploinsufficient DDX41 expression. DDX41 lesions caused altered pre-mRNA splicing and RNA processing. DDX41 is exemplary of Other RNA helicase genes also affected by somatic mutations, suggesting that they constitute a family of tumor suppressor genes.

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