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

• Published in: Genes chromosomes & cancer Vol. 63; no. 5; pp. e23242 - n/a
• Main Authors: Ragnarsson, Charlotte, Yang, Minjun, Moura‐Castro, Larissa Helena, Aydın, Efe, Gunnarsson, Rebeqa, Olsson‐Arvidsson, Linda, Lilljebjörn, Henrik, Fioretos, Thoas, Duployez, Nicolas, Zaliova, Marketa, Zuna, Jan, Castor, Anders, Johansson, Bertil, Paulsson, Kajsa
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.05.2024; Wiley Subscription Services, Inc
• Subjects: Acute lymphoblastic leukemia; Alleles; ARID5B variants; B-cell precursor acute lymphoblastic leukemia; Cancer and Oncology; Cancer och onkologi; Child; Child, Preschool; Chromosome 10; Clinical Medicine; constitutional; DNA-Binding Proteins - genetics; Female; Genetic diversity; high hyperdiploidy; Humans; Klinisk medicin; Leukemia; Leukemogenesis; Lymphatic leukemia; Male; Medical and Health Sciences; Medicin och hälsovetenskap; pediatric; Pediatrics; Polymorphism, Single Nucleotide; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Single-nucleotide polymorphism; somatic; Transcription Factors - genetics; B‐cell precursor acute lymphoblastic leukemia; constitutional; somatic; ARID5B variants; high hyperdiploidy; pediatric
• ISSN: 1045-2257; 1098-2264; 1098-2264
• DOI: 10.1002/gcc.23242

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.