Research Papers:

Targeted ultra-deep sequencing reveals recurrent and mutually exclusive mutations of cancer genes in blastic plasmacytoid dendritic cell neoplasm

Albrecht Stenzinger _, Volker Endris, Nicole Pfarr, Mindaugas Andrulis, Korinna Jöhrens, Frederick Klauschen, Udo Siebolts, Thomas Wolf, Philipp-Sebastian Koch, Miriam Schulz, Wolfgang Hartschuh, Sergij Goerdt, Jochen K. Lennerz, Claudia Wickenhauser, Wolfram Klapper, Ioannis Anagnostopoulos and Wilko Weichert

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Oncotarget. 2014; 5:6404-6413. https://doi.org/10.18632/oncotarget.2223

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Albrecht Stenzinger1,*, Volker Endris1,*, Nicole Pfarr1, Mindaugas Andrulis1, Korinna Jöhrens2, Frederick Klauschen2, Udo Siebolts3, Thomas Wolf1, Philipp-Sebastian Koch4, Miriam Schulz5, Wolfgang Hartschuh6, Sergij Goerdt4, Jochen K. Lennerz7, Claudia Wickenhauser3, Wolfram Klapper8, Ioannis Anagnostopoulos2,** and Wilko Weichert1,9,**

1 Institute of Pathology, University Hospital Heidelberg, Germany

2 Institute of Pathology, Charité University Hospital, Berlin, Germany

3 Institute of Pathology, University Hospital Halle and Institute of Pathology, University Hospital Leipzig, Germany

4 Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

5 German Red Cross Blood Service and Institute for Transfusion Medicine and Immunohematology, Goethe University Medical School, Frankfurt, Germany

6 Department of Dermatology, University Hospital Heidelberg, Germany

7 Institute of Pathology, University of Ulm, Ulm, Germany

8 Department of Pathology, Hematopathology Section and Lymph Node Registry, Christian-Albrechts-University of Kiel, Germany

9 National Center for Tumor Diseases, Heidelberg, Germany

10 Present address: Harvard Medical School, Massachusetts General Hospital, Department of Pathology, Boston, MA, USA

* These authors contributed equally to this work

** These authors share last authorship


Albrecht Stenzinger , email:

Ioannis Anagnostopoulos, email:

Keywords: blastic plasmacytoid dendritic cell neoplasm, BPDCN, recurrent mutations, mutually exclusive mutations, next generation sequencing, ATM, KRAS, NRAS, CDKN2A

Received: May 20, 2014 Accepted: July 15, 2014 Published: July 16, 2014


Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1% each), as well as in VHL, BRAF, MLH1, TP53 and RET (3% each). Moreover, NRAS, KRAS and ATM mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored.

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