Rare TCF3 variants associated with pediatric B cell acute lymphoblastic leukemia

• Published in: Pediatric hematology and oncology 2024, Vol.41 (1), p.81-87
• Main Authors: Miyamoto, Satoshi, Urayama, Kevin Y, Arakawa, Yuki, Koh, Katsuyoshi, Yuza, Yuki, Hasegawa, Daisuke, Taneyama, Yuichi, Noguchi, Yasushi, Yanagimachi, Masakatsu, Inukai, Takeshi, Ota, Setsuo, Takahashi, Hiroyuki, Keino, Dai, Toyama, Daisuke, Takita, Junko, Tomizawa, Daisuke, Morio, Tomohiro, Koike, Kazutoshi, Moriwaki, Koichi, Sato, Yuya, Fujimura, Junya, Morita, Daisuke, Sekinaka, Yujin, Nakamura, Kozue, Sakashita, Kazuo, Goto, Hiroaki, Manabe, Atsushi, Takagi, Masatoshi
• Format: Article
• Language: English
• ISSN: 0888-0018; 1521-0669
• DOI: 10.1080/08880018.2023.2201302

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. and , 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 , 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 gene-based evaluation, the numbers of rare deleterious germline sequence variants in patients with pediatric B-ALL were compared with those in cancer-free individuals using data in public databases. As a single-variant evaluation, the frequencies of rare deleterious germline sequence variants in patients with pediatric B-ALL were also compared with those in control data. gene-based analysis revealed significant associations between rare deleterious variants and pediatric B-ALL development. In addition, variant-based analysis showed particularly strong association between variant rs372168347 (three in 521 TCCSG and three in the 15780 gnomAD whole genome analysis cohort,  = 0.0006) and pediatric B-ALL development. variants are known to influence B cell maturation and may increase the risk of preleukemic clone emergence.