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

  • 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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Author:Albrecht StenzingerORCiDGND, 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, Wilko Weichert
Pubmed Id:
Parent Title (English):Oncotarget
Publisher:Impact Journals LLC
Place of publication:[S.l.]
Document Type:Article
Date of Publication (online):2014/07/16
Date of first Publication:2014/07/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/11/22
Tag:ATM; BPDCN; CDKN2A; KRAS; NRAS; blastic plasmacytoid dendritic cell neoplasm; mutually exclusive mutations; next generation sequencing; recurrent mutations
Page Number:10
First Page:6404
Last Page:6413
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 3.0