The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

Constitutional and acquired genetic variants in ARID5B in pediatric B-cell precursor acute lymphoblastic leukemia

Author

  • Charlotte Ragnarsson
  • Minjun Yang
  • Larissa Helena Moura-Castro
  • Efe Aydın
  • Rebeqa Gunnarsson
  • Linda Olsson-Arvidsson
  • Henrik Lilljebjörn
  • Thoas Fioretos
  • Nicolas Duployez
  • Marketa Zaliova
  • Jan Zuna
  • Anders Castor
  • Bertil Johansson
  • Kajsa Paulsson
Show all

Summary, in English

Constitutional polymorphisms in ARID5B are associated with an increased risk of developing high hyperdiploid (HeH; 51–67 chromosomes) pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). Here, we investigated constitutional and somatic ARID5B variants in 1335 BCP ALL cases from five different cohorts, with a particular focus on HeH cases. In 353 HeH ALL that were heterozygous for risk alleles and trisomic for chromosome 10, where ARID5B is located, a significantly higher proportion of risk allele duplication was seen for the SNPs rs7090445 (p = 0.009), rs7089424 (p = 0.005), rs7073837 (p = 0.03), and rs10740055 (p = 0.04). Somatic ARID5B deletions were seen in 16/1335 cases (1.2%), being more common in HeH than in other genetic subtypes (2.2% vs. 0.4%; p = 0.002). The expression of ARID5B in HeH cases with genomic deletions was reduced, consistent with a functional role in leukemogenesis. Whole-genome sequencing and RNA-sequencing in HeH revealed additional somatic events involving ARID5B, resulting in a total frequency of 3.6% of HeH cases displaying a somatic ARID5B aberration. Overall, our results show that both constitutional and somatic events in ARID5B are involved in the leukemogenesis of pediatric BCP ALL, particularly in the HeH subtype.

Department/s

  • Division of Clinical Genetics
  • Aneuploidy in cancer
  • LUCC: Lund University Cancer Centre
  • Genetic and epigenetic studies of pediatric leukemia
  • Translational Genomic and Functional Studies of Leukemia
  • LTH Profile Area: Engineering Health

Publishing year

2024

Language

English

Publication/Series

Genes Chromosomes and Cancer

Volume

63

Issue

5

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Cancer and Oncology

Keywords

  • ARID5B variants
  • B-cell precursor acute lymphoblastic leukemia
  • constitutional
  • high hyperdiploidy
  • pediatric
  • somatic

Status

Published

Research group

  • Aneuploidy in cancer
  • Genetic and epigenetic studies of pediatric leukemia
  • Translational Genomic and Functional Studies of Leukemia

ISBN/ISSN/Other

  • ISSN: 1045-2257