Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanics

Maoxiang Qian, Heng Xu, Virginia Perez-Andreu, Kathryn G. Roberts, Hui Zhang, Wenjian Yang, Shouyue Zhang, Xujie Zhao, Colton Smith, Meenakshi Devidas, Julie M. Gastier-Foster, Elizabeth Raetz, Eric Larsen, Esteban G. Burchard, Naomi Winick, W. Paul Bowman, Paul L. Martin, Michael Borowitz, Brent Wood, Federico Antillon-KlussmannChing Hon Pui, Charles G. Mullighan, William E. Evans, Stephen P. Hunger, Mary V. Relling, Mignon L. Loh, Jun J. Yang

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Characterized by high levels of Native American ancestry, Hispanics are disproportionally affected by this cancer with high incidence and inferior survival. However, the genetic basis for this disparity remains poorly understood because of a paucity of genome-wide investigation of ALL in Hispanics. Performing a genome-wide association study (GWAS) in 940 Hispanic children with ALL and 681 ancestry-matched non-ALL controls, we identified a novel susceptibility locus in the ERG gene (rs2836365; P 5 3.76 3 102 8 ; odds ratio [OR] 5 1.56), with independent validation (P 5 .01; OR 5 1.43). Imputation analyses pointed to a single causal variant driving the association signal at this locus overlapping with putative regulatory DNA elements. The effect size of the ERG risk variant rose with increasing Native American genetic ancestry. The ERG risk genotype was underrepresented in ALL with the ETV6-RUNX1 fusion (P < .0005) but enriched in the TCF3-PBX1 subtype (P < .05). Interestingly, ALL cases with germline ERG risk alleles were significantly less likely to have somatic ERG deletion (P < .05). Our results provide novel insights into genetic predisposition to ALL and its contribution to racial disparity in this cancer.

Original languageEnglish (US)
Pages (from-to)724-729
Number of pages6
JournalBlood
Volume133
Issue number7
DOIs
StatePublished - Feb 14 2019

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Qian, M., Xu, H., Perez-Andreu, V., Roberts, K. G., Zhang, H., Yang, W., Zhang, S., Zhao, X., Smith, C., Devidas, M., Gastier-Foster, J. M., Raetz, E., Larsen, E., Burchard, E. G., Winick, N., Paul Bowman, W., Martin, P. L., Borowitz, M., Wood, B., ... Yang, J. J. (2019). Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanics. Blood, 133(7), 724-729. https://doi.org/10.1182/blood-2018-07-862946