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.
Highlights
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an orphan disease with a very aggressive clinical course resulting in median survival times of 12-14 months [1,2]
Named blastic NK/T cell lymphoma or agranular CD4+/CD56+ hematodermic neoplasm/tumour [6, 9, 10, 11], BPDCN is –according to the current WHO classification- classified as an acute myeloid leukemiarelated precursor neoplasm [12] that has been shown to derive from precursors of plasmacytoid dendritic cells [13, 14,15, 16]
Thirty-three cases of BPDCN were analyzed for somatic mutations of 50 common cancer genes by ultradeep targeted semiconductor-based massive parallel sequencing
Summary
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an orphan disease with a very aggressive clinical course resulting in median survival times of 12-14 months [1,2]. Named blastic NK/T cell lymphoma or agranular CD4+/CD56+ hematodermic neoplasm/tumour [6, 9, 10, 11], BPDCN is –according to the current WHO classification- classified as an acute myeloid leukemiarelated precursor neoplasm [12] that has been shown to derive from precursors of plasmacytoid dendritic cells [13, 14,15, 16]. As with other rare diseases, the low prevalence of BPDCN and its only quite recent recognition as a distinct tumour entity are major obstacles for comprehensive and systematic clinical and biological research efforts. To complement previous efforts and to gain more insight into the genetic basis of BPDCN, we performed targeted ultra-deep semiconductor-based massive parallel sequencing of 50 cancer-related genes [23] in 33 formalinfixed, paraffin embedded primary BPDCN samples and assayed CDKN2A copy numbers
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