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

Ragnarsson, Charlotte LU ; Yang, Minjun LU ; Moura-Castro, Larissa Helena LU orcid ; Aydın, Efe LU ; Gunnarsson, Rebeqa LU ; Olsson-Arvidsson, Linda LU ; Lilljebjörn, Henrik LU orcid ; Fioretos, Thoas LU ; Duployez, Nicolas and Zaliova, Marketa , et al. (2024) In Genes Chromosomes and Cancer 63(5).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ARID5B variants, B-cell precursor acute lymphoblastic leukemia, constitutional, high hyperdiploidy, pediatric, somatic
in
Genes Chromosomes and Cancer
volume
63
issue
5
article number
e23242
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85192934050
  • pmid:38738968
ISSN
1045-2257
DOI
10.1002/gcc.23242
language
English
LU publication?
yes
id
fd1aac37-db36-4d76-97b2-87b0e31f23e6
date added to LUP
2024-05-27 14:29:47
date last changed
2024-06-24 17:20:25
@article{fd1aac37-db36-4d76-97b2-87b0e31f23e6,
  abstract     = {{<p>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.</p>}},
  author       = {{Ragnarsson, Charlotte and Yang, Minjun and Moura-Castro, Larissa Helena and Aydın, Efe and Gunnarsson, Rebeqa and Olsson-Arvidsson, Linda and Lilljebjörn, Henrik and Fioretos, Thoas and Duployez, Nicolas and Zaliova, Marketa and Zuna, Jan and Castor, Anders and Johansson, Bertil and Paulsson, Kajsa}},
  issn         = {{1045-2257}},
  keywords     = {{ARID5B variants; B-cell precursor acute lymphoblastic leukemia; constitutional; high hyperdiploidy; pediatric; somatic}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Genes Chromosomes and Cancer}},
  title        = {{Constitutional and acquired genetic variants in ARID5B in pediatric B-cell precursor acute lymphoblastic leukemia}},
  url          = {{http://dx.doi.org/10.1002/gcc.23242}},
  doi          = {{10.1002/gcc.23242}},
  volume       = {{63}},
  year         = {{2024}},
}