title: Targeted ultra-deep sequencing reveals recurrent and mutually exclusive mutations of cancer genes in blastic plasmacytoid dendritic cell neoplasm.
abstract: 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%), as well as in VHL, BRAF, MLH1, TP53 and RET1 (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.
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Germany; These authors contributed equally to this work.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stenzinger
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Germany; These authors contributed equally to this work.
authors.forename: Volker
authors.initials: V
authors.lastname: Endris
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pfarr
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Germany.
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Andrulis
authors.affiliation: Institute of Pathology, Charité University Hospital, Berlin, Germany.
authors.forename: Korinna
authors.initials: K
authors.lastname: Jöhrens
authors.affiliation: Institute of Pathology, Charité University Hospital, Berlin, Germany.
authors.forename: Frederick
authors.initials: F
authors.lastname: Klauschen
authors.affiliation: Institute of Pathology, University Hospital Halle and Institute of Pathology, University Hospital Leipzig, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Siebolts
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wolf
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Philipp-Sebastian
authors.initials: PS
authors.lastname: Koch
authors.affiliation: German Red Cross Blood Service and Institute for Transfusion Medicine and Immunohematology, Goethe University Medical School, Frankfurt, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Schulz
authors.affiliation: Department of Dermatology, University Hospital Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hartschuh
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Sergij
authors.initials: S
authors.lastname: Goerdt
authors.affiliation: Institute of Pathology, University of Ulm, Ulm, Germany.
authors.forename: Jochen K
authors.initials: JK
authors.lastname: Lennerz
authors.affiliation: Institute of Pathology, University Hospital Halle and Institute of Pathology, University Hospital Leipzig, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Wickenhauser
authors.affiliation: Department of Pathology, Hematopathology Section and Lymph Node Registry, Christian-Albrechts-University of Kiel, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.affiliation: Institute of Pathology, Charité University Hospital, Berlin, Germany;
authors.forename: Ioannis
authors.initials: I
authors.lastname: Anagnostopoulos
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Germany; National Center for Tumor Diseases, Heidelberg, Germany; These authors contributed equally to this work.
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001752:Blast Crisis / Q000473:pathology*; D004252:DNA Mutational Analysis / Q000379:methods; D003713:Dendritic Cells / Q000473:pathology*; D005260:Female; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010954:Plasmacytoma / Q000473:pathology*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*