Genomic aberrations involving 12p/ETV6 are highly prevalent in blastic plasmacytoid dendritic cell neoplasms and might represent early clonal events

Leuk Res. 2018 Oct:73:86-94. doi: 10.1016/j.leukres.2018.09.006. Epub 2018 Sep 17.

Abstract

Background: Chromosomal aberrations at the ETV6 gene locus on 12p13.2 are common in bone marrow samples involved by blastic plasmacytoid dendritic cell neoplasm (BPDCN). However, their pathogenic role, incidence in cutaneous BPDCN lesions, and clinical significance have not been assessed systematically.

Results: The study group included 30 BPDCN patients, 25 men and 5 women, with a median age of 64 years. Conventional cytogenetic analysis demonstrated karyotypic aberrancies in 15 cases, of which 8 had chromosomal lesions involving 12p. In addition, 2 cases with normal diploid karyotype had cryptic 12p/ETV6 deletion by ETV6 FISH test. Notably, 2 bone marrow samples with ETV6 rearrangement had no detectable BPDCN involvement, but otherwise dynamic changes in the detection of 12p/ETV6 aberrations correlated with the presence of morphologically and/or immunophenotypically detectable disease. Tissue specimens from 6 patients with cutaneous BPDCN all tested positive for homozygous or heterozygous ETV6 deletions.

Conclusion: We demonstrate that monoallelic and biallelic 12p/ETV6 deletions are highly prevalent in BPDCN, and their detection is enhanced by the use of FISH and aCGH. In addition, 12p/ETV6 may be present in the bone marrow of BPDCN patients in the absence of detectable disease suggesting that such alterations might represent an early pathogenic event.

Keywords: 12p/ETV6 aberration; Blastic plasmacytoid dendritic cell neoplasm (BPDCN); Fluorescence in situ hybridization (FISH); aCGH.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 12 / genetics*
  • Chromosomes, Human, Pair 12 / metabolism
  • Dendritic Cells*
  • ETS Translocation Variant 6 Protein
  • Female
  • Gene Deletion*
  • Hematologic Neoplasms / genetics*
  • Hematologic Neoplasms / metabolism
  • Humans
  • Male
  • Middle Aged
  • Prevalence
  • Proto-Oncogene Proteins c-ets / genetics*
  • Proto-Oncogene Proteins c-ets / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism

Substances

  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins