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Lookup NU author(s): Professor James Allan,
Professor Anthony Moorman
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019, The Author(s).There is increasing evidence for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children. To identify new risk variants for B-cell ALL (B-ALL) we conducted a meta-analysis with four GWAS (genome-wide association studies), totalling 5321 cases and 16,666 controls of European descent. We herein describe novel risk loci for B-ALL at 9q21.31 (rs76925697, P = 2.11 × 10−8), for high-hyperdiploid ALL at 5q31.1 (rs886285, P = 1.56 × 10−8) and 6p21.31 (rs210143 in BAK1, P = 2.21 × 10−8), and ETV6-RUNX1 ALL at 17q21.32 (rs10853104 in IGF2BP1, P = 1.82 × 10−8). Particularly notable are the pleiotropic effects of the BAK1 variant on multiple haematological malignancies and specific effects of IGF2BP1 on ETV6-RUNX1 ALL evidenced by both germline and somatic genomic analyses. Integration of GWAS signals with transcriptomic/epigenomic profiling and 3D chromatin interaction data for these leukaemia risk loci suggests deregulation of B-cell development and the cell cycle as central mechanisms governing genetic susceptibility to ALL.
Author(s): Vijayakrishnan J, Qian M, Studd JB, Yang W, Kinnersley B, Law PJ, Broderick P, Raetz EA, Allan J, Pui C-H, Vora A, Evans WE, Moorman A, Yeoh A, Yang W, Li C, Bartram CR, Mullighan CG, Zimmerman M, Hunger SP, Schrappe M, Relling MV, Stanulla M, Loh ML, Houlston RS, Yang JJ
Publication type: Article
Publication status: Published
Journal: Nature Communications
Online publication date: 25/11/2019
Acceptance date: 17/10/2019
Date deposited: 09/12/2019
ISSN (electronic): 2041-1723
Publisher: Nature Research
PubMed id: 31767839
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