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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia

Author

  • Rebeqa Gunnarsson
  • Sebastian Dilorenzo
  • Kristina B. Lundin-Ström
  • Linda Olsson
  • Andrea Biloglav
  • Henrik Lilljebjörn
  • Marianne Rissler
  • Per Wahlberg
  • Anders Lundmark
  • Anders Castor
  • Mikael Behrendtz
  • Thoas Fioretos
  • Kajsa Paulsson
  • Anders Isaksson
  • Bertil Johansson
Show all

Summary, in English

High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. 35%; P = 0.42). Only 0.6% of the 36,259 CpGs on 1q were differentially methylated between cases w (n = 14)/wo (n = 13) dup(1q). RNA sequencing of high hyperdiploid (HeH) and t(1;19)(q23;p13)-positive cases w (n = 14)/wo (n = 52) dup(1q) identified 252 and 424 differentially expressed genes, respectively; only seven overlapped. Of the overexpressed genes in the HeH and t(1;19) groups, 23 and 31%, respectively, mapped to 1q; 60-80% of these encode nucleic acid/protein binding factors or proteins with catalytic activity. We conclude that the pathogenetically important consequence of dup(1q) in BCP ALL is a gene-dosage effect, with the deregulated genes differing between genetic subtypes, but involving similar molecular functions, biological processes, and protein classes.

Department/s

  • Division of Clinical Genetics
  • Paediatrics (Lund)

Publishing year

2018-03-12

Language

English

Pages

2117-2125

Publication/Series

Leukemia

Volume

32

Issue

10

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology
  • Medical Genetics

Status

Published

ISBN/ISSN/Other

  • ISSN: 0887-6924