@article{e298ab72ef464f3ba5dff83c6665ba24,
title = "Identification of four novel associations for B-cell acute lymphoblastic leukaemia risk",
abstract = "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 = "Jayaram Vijayakrishnan and Maoxiang Qian and Studd, {James B.} and Wenjian Yang and Ben Kinnersley and Law, {Philip J.} and Peter Broderick and Raetz, {Elizabeth A.} and James Allan and Pui, {Ching Hon} and Ajay Vora and Evans, {William E.} and Anthony Moorman and Allen Yeoh and Wentao Yang and Chunliang Li and Bartram, {Claus R.} and Mullighan, {Charles G.} and Martin Zimmerman and Hunger, {Stephen P.} and Martin Schrappe and Relling, {Mary V.} and Martin Stanulla and Loh, {Mignon L.} and Houlston, {Richard S.} and Yang, {Jun J.}",
note = "Funding Information: In the UK, funding was provided by Bloodwise and Cancer Research UK (C1298/A8362). In the United States, this work was partly supported by National Institutes of Health Grant Numbers CA21765, CA98543, CA114766, CA98413, CA180886, CA180899, GM92666, GM115279, and GM097119, and the American Lebanese Syrian Associated Charities. We thank the patients and parents who participated in the Children{\textquoteright}s Oncology Group (COG) protocols included in this study, the clinicians and research staff at St. Jude Children{\textquoteright}s Research Hospital and COG institutions, Jeanette Pullen (University of Mississippi, Jackson, MS) for assistance in the classification of patients with ALL and Mark Shriver (Pennsylvania State University, University Park, PA) for sharing single-nucleotide polymorphism genotype data of the Native American references. M.Q. is supported by the Initial Funding for New PI of Fudan University, the National Natural Science Foundation of China (81973997) and the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning. S.P.H. is the Jeffrey E. Perelman Distinguished Chair in Pediatrics at The Children{\textquoteright}s Hospital of Philadelphia. M.L.L. is the University of California, San Francisco Benioff Chair of Children{\textquoteright}s Health and the Deborah and Arthur Ablin Chair of Pediatric Molecular Oncology. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-13069-6",
language = "English (US)",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}