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Epigenetic matrix and targeted therapy of BPDCN
Results
Whole-exome sequencing reveals the epigenetic pro- gram dysregulation as the main theme of the blastic plasmacytoid dendritic cell neoplasm mutational landscape
We collected 14 BPDCN cases with a mean age of 56 years at diagnosis (range 9-89 years), a male-to-female
ratio of 10:4, and the classical BPDCN presentation (Online Supplementary Tables S1 and S2).1 The enrolled patients underwent different treatment regimens and 78.5% (11 out of 14) died of the disease 6.3-76 months after the diag- nosis or were lost at follow up. Most patients who under- went autologous and/or allogeneic hematopoietic stem cell transplantation experienced a prolonged survival.
We performed WES on 14 BPDCN cases, and on the
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Figure 1. The genomic characterization of blastic plasmacy- toid dendritic cell neoplasm (BPDCN). (A) Circos plot graphi- cal representation of the functional analysis performed on 54 genes recurrently mutated and/or affected by nonsense and frameshift single nucleotide variants (SNVs) in BPDCN whole-exome sequencing (WES) samples. The four biological processes most significantly enriched are reported in the counterclockwise order from the highest to the lowest P-value: the gamma-aminobutyric acid (GABA) secretion (in violet), the Rac signaling (in red), the hematopoietic stem cell homeostasis (in light blue) and the epigenetic process (in green). The genes are colored according to their belonging to one or more of the biological processes represented. Genes not involved are in gray. (B) Overview of the TET2 and ASXL1 mutations identified. Structure of ASXL1 protein with C-termi- nal plant homeodomain catalytic region and structure of TET2 protein showing the catalytic core region: the cysteine- rich (Cys) and double-stranded β-helix (DSBH) domains. Empty circles: somatic SNVs. + : frameshift SNV; *nonsense SNV. (C) Heatmap representation of SNVs in BPDCN WES samples and its distribution among selected pathways com- monly mutated in myeloid disorders. The SNVs, the affected genes and the related pathways are reported in rows, while, the BPDCN samples are in columns.
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