Stenzinger, AlbrechtEndris, VolkerPfarr, NicoleAndrulis, MindaugasJöhrens, KorinnaKlauschen, FrederickSiebolts, UdoWolf, ThomasKoch, Philipp-SebastianSchulz, MiriamHartschuh, WolfgangGoerdt, SergijLennerz, Jochen K.Wickenhauser, ClaudiaKlapper, WolframAnagnostopoulos, IoannisWeichert, Wilko2014-10-012014Stenzinger, A., V. Endris, N. Pfarr, M. Andrulis, K. Jöhrens, F. Klauschen, U. Siebolts, et al. 2014. “Targeted ultra-deep sequencing reveals recurrent and mutually exclusive mutations of cancer genes in blastic plasmacytoid dendritic cell neoplasm.” Oncotarget 5 (15): 6404-6413.1949-2553http://nrs.harvard.edu/urn-3:HUL.InstRepos:12987352Blastic 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.en-USblastic plasmacytoid dendritic cell neoplasmBPDCNrecurrent mutationsmutually exclusive mutationsnext generation sequencingATMKRASNRASCDKN2AJournal Article2014-10-0110.18632/oncotarget.2223