Whole-genome analysis uncovers recurrent IKZF1 inactivation and aberrant cell adhesion in blastic plasmacytoid dendritic cell neoplasm

Armando N. Bastidas Torres, Davy Cats, Hailiang Mei, Daniele Fanoni, Jessica Gliozzo, Laura Corti, Marco Paulli, Maarten H. Vermeer, Rein Willemze, Emilio Berti, Cornelis P. Tensen

Research output: Contribution to journalArticlepeer-review


Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematological malignancy with a poorly understood pathobiology and no effective therapeutic options. Despite a few recurrent genetic defects (eg, single nucleotide changes, indels, large chromosomal aberrations) have been identified in BPDCN, none are disease-specific, and more importantly, none explain its genesis or clinical behavior. In this study, we performed the first high resolution whole-genome analysis of BPDCN with a special focus on structural genomic alterations by using whole-genome sequencing and RNA sequencing. Our study, the first to characterize the landscape of genomic rearrangements and copy number alterations of BPDCN at nucleotide-level resolution, revealed that IKZF1, a gene encoding a transcription factor required for the differentiation of plasmacytoid dendritic cell precursors, is focally inactivated through recurrent structural alterations in this neoplasm. In concordance with the genomic data, transcriptome analysis revealed that conserved IKZF1 target genes display a loss-of-IKZF1 expression pattern. Furthermore, up-regulation of cellular processes responsible for cell-cell and cell-ECM interactions, which is a hallmark of IKZF1 deficiency, was prominent in BPDCN. Our findings suggest that IKZF1 inactivation plays a central role in the pathobiology of the disease, and consequently, therapeutic approaches directed at reestablishing the function of this gene might be beneficial for patients.

Original languageEnglish
Pages (from-to)295-308
JournalGenes Chromosomes and Cancer
Issue number5
Publication statusPublished - 2020


  • blastic plasmacytoid dendritic cell neoplasm
  • cell adhesion
  • cutaneous lymphoma
  • Ikaros
  • IKZF1
  • RNA sequencing
  • whole-genome sequencing

ASJC Scopus subject areas

  • Genetics
  • Cancer Research


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