Please use this identifier to cite or link to this item: https://doi.org/10.1093/jnci/djaa133
Title: Genome-Wide Association Study of Susceptibility Loci for TCF3-PBX1 Acute Lymphoblastic Leukemia in Children
Authors: Lee, SHR 
Qian, M
Yang, W
Diedrich, JD
Raetz, E
Yang, W
Dong, Q
Devidas, M
Pei, D
Yeoh, A 
Cheng, C
Pui, CH
Evans, WE
Mullighan, CG
Hunger, SP
Savic, D
Relling, MV
Loh, ML
Yang, JJ
Issue Date: 1-Jul-2021
Publisher: Oxford University Press (OUP)
Citation: Lee, SHR, Qian, M, Yang, W, Diedrich, JD, Raetz, E, Yang, W, Dong, Q, Devidas, M, Pei, D, Yeoh, A, Cheng, C, Pui, CH, Evans, WE, Mullighan, CG, Hunger, SP, Savic, D, Relling, MV, Loh, ML, Yang, JJ (2021-07-01). Genome-Wide Association Study of Susceptibility Loci for TCF3-PBX1 Acute Lymphoblastic Leukemia in Children. Journal of the National Cancer Institute 113 (7) : 933-937. ScholarBank@NUS Repository. https://doi.org/10.1093/jnci/djaa133
Abstract: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. TCF3-PBX1 fusion defines a common molecular subtype of ALL with unique clinical features, but the molecular basis of its inherited susceptibility is unknown. In a genome-wide association study of 1494 ALL cases and 2057 non-ALL controls, we identified a germline risk locus located in an intergenic region between BCL11A and PAPOLG: rs2665658, P = 1.88 × 10-8 for TCF3-PBX1 ALL vs non-ALL, and P = 1.70 × 10-8 for TCF3-PBX1 ALL vs other-ALL. The lead variant was validated in a replication cohort, and conditional analyses pointed to a single causal variant with subtype-specific effect. The risk variant is located in a regulatory DNA element uniquely activated in ALL cells with the TCF3-PBX1 fusion and may distally modulate the transcription of the adjacent gene REL. Our results expand the understanding of subtype-specific ALL susceptibility and highlight plausible interplay between germline variants and somatic genomic abnormalities in ALL pathogenesis.
Source Title: Journal of the National Cancer Institute
URI: https://scholarbank.nus.edu.sg/handle/10635/206751
ISSN: 00278874
14602105
DOI: 10.1093/jnci/djaa133
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