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

Autor: Ragnarsson C; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.; Department of Paediatrics, Skåne University Hospital, Lund University, Lund, Sweden., Yang M; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden., Moura-Castro LH; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden., Aydın E; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden., Gunnarsson R; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden., Olsson-Arvidsson L; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.; Department of Clinical Genetics, Pathology, and Molecular Diagnostics, Office for Medical Services, Region Skåne, Lund, Sweden., Lilljebjörn H; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden., Fioretos T; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.; Department of Clinical Genetics, Pathology, and Molecular Diagnostics, Office for Medical Services, Region Skåne, Lund, Sweden., Duployez N; Laboratory of Haematology, Centre Hospitalier Universitaire (CHU) Lille, University of Lille, INSERM Unité 1277 Canther, Lille, France., Zaliova M; Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.; Childhood Leukaemia Investigation Prague (CLIP), Prague, Czech Republic., Zuna J; Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University/University Hospital Motol, Prague, Czech Republic.; Childhood Leukaemia Investigation Prague (CLIP), Prague, Czech Republic., Castor A; Department of Paediatrics, Skåne University Hospital, Lund University, Lund, Sweden., Johansson B; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.; Department of Clinical Genetics, Pathology, and Molecular Diagnostics, Office for Medical Services, Region Skåne, Lund, Sweden., Paulsson K; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Jazyk: angličtina
Zdroj: Genes, chromosomes & cancer [Genes Chromosomes Cancer] 2024 May; Vol. 63 (5), pp. e23242.
DOI: 10.1002/gcc.23242
Abstrakt: 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.
(© 2024 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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