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Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Menezes J
  • Acquadro F
  • Wiseman M
  • Gómez-López G
  • Salgado RN
  • Talavera-Casañas JG
  • Buño I
  • Montes-Moreno S
  • Hernández-Rivas JM
  • Ayala R
  • Calasanz MJ
  • Larrayoz MJ
  • Brichs LF
  • Gonzalez-Vicent M
  • Pisano DG
  • Piris MA
  • Álvarez S
  • Cigudosa JC

Grupos

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare disease that currently lacks genomic and genetic biomarkers to assist in its clinical management. We performed whole-exome sequencing (WES) of three BPDCN cases. Based on these data, we designed a resequencing approach to identify mutations in 38 selected genes in 25 BPDCN samples. WES revealed 37-99 deleterious gene mutations per exome with no common affected genes between patients, but with clear overlap in terms of molecular and disease pathways (hematological and dermatological disease). We identified for the first time deleterious mutations in IKZF3, HOXB9, UBE2G2 and ZEB2 in human leukemia. Target sequencing identified 29 recurring genes, ranging in prevalence from 36% for previously known genes, such as TET2, to 12-16% for newly identified genes, such as IKZF3 or ZEB2. Half of the tumors had mutations affecting either the DNA methylation or chromatin remodeling pathways. The clinical analysis revealed that patients with mutations in DNA methylation pathway had a significantly reduced overall survival (P= 0.047). We provide the first mutational profiling of BPDCN. The data support the current WHO classification of the disease as a myeloid disorder and provide a biological rationale for the incorporation of epigenetic therapies for its treatment.

Datos de la publicación

ISSN/ISSNe:
0887-6924, 1476-5551

LEUKEMIA  SPRINGERNATURE

Tipo:
Article
Páginas:
823-829
PubMed:
24072100
Factor de Impacto:
4,657 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 139

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Keywords

  • BPDCN; blastic NK-cell lymphoma; TET2; ASXL1; IKAROS family

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