Constitutional and acquired genetic variants in ARID5B in pediatric B-cell precursor acute lymphoblastic leukemia
(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.
(Less)
- author
- organization
- publishing date
- 2024
- 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
-
- pmid:38738968
- scopus:85192934050
- 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}}, }