Rare TCF3 variants associated with pediatric B cell acute lymphoblastic leukemia.
Pediatr Hematol Oncol
; 41(1): 81-87, 2024.
Article
en En
| MEDLINE
| ID: mdl-37129918
ABSTRACT
Germline genetic variants influence development of pediatric B cell acute lymphoblastic leukemia (B-ALL). Genome-wide association studies (GWAS) have identified several pediatric B-ALL susceptibility loci. IKZF1 and PAX5, transcription factors involved in B cell development, have been reported as susceptibility genes for B-ALL development. Therefore, we hypothesized that rare variants of genes involved in B cell development would be candidate susceptibility loci for pediatric B-ALL. Thus, we sequenced TCF3, a key transcription factor gene involving in B cell development. Saliva DNA from 527 pediatric patients with pediatric B-ALL in remission who were registered with the Tokyo Children's Cancer Study Group (TCCSG) were examined. As a TCF3 gene-based evaluation, the numbers of rare deleterious germline TCF3 sequence variants in patients with pediatric B-ALL were compared with those in cancer-free individuals using data in public databases. As a TCF3 single-variant evaluation, the frequencies of rare deleterious germline TCF3 sequence variants in patients with pediatric B-ALL were also compared with those in control data. TCF3 gene-based analysis revealed significant associations between rare deleterious variants and pediatric B-ALL development. In addition, TCF3 variant-based analysis showed particularly strong association between variant rs372168347 (three in 521 TCCSG and three in the 15780 gnomAD whole genome analysis cohort, p = 0.0006) and pediatric B-ALL development. TCF3 variants are known to influence B cell maturation and may increase the risk of preleukemic clone emergence.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Leucemia-Linfoma Linfoblástico de Células Precursoras B
/
Linfoma de Burkitt
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Child
/
Humans
Idioma:
En
Revista:
Pediatr Hematol Oncol
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón