Open Access

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, Wilko Weichert

• 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.