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

Publication ,  Journal Article
Qian, M; Xu, H; Perez-Andreu, V; Roberts, KG; Zhang, H; Yang, W; Zhang, S; Zhao, X; Smith, C; Devidas, M; Gastier-Foster, JM; Raetz, E ...
Published in: Blood
February 14, 2019

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 = 3.76 × 10-8; odds ratio [OR] = 1.56), with independent validation (P = .01; OR = 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.

Duke Scholars

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

February 14, 2019

Volume

133

Issue

7

Start / End Page

724 / 729

Location

United States

Related Subject Headings

  • Transcriptional Regulator ERG
  • Prognosis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Polymorphism, Single Nucleotide
  • Oncogene Proteins, Fusion
  • Male
  • Immunology
  • Humans
  • Hispanic or Latino
  • Genotype
 

Citation

APA
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MLA
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Qian, M., Xu, H., Perez-Andreu, V., Roberts, K. G., Zhang, H., Yang, W., … 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
Qian, Maoxiang, Heng Xu, Virginia Perez-Andreu, Kathryn G. Roberts, Hui Zhang, Wenjian Yang, Shouyue Zhang, et al. “Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanics.Blood 133, no. 7 (February 14, 2019): 724–29. https://doi.org/10.1182/blood-2018-07-862946.
Qian M, Xu H, Perez-Andreu V, Roberts KG, Zhang H, Yang W, et al. Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanics. Blood. 2019 Feb 14;133(7):724–9.
Qian, Maoxiang, et al. “Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanics.Blood, vol. 133, no. 7, Feb. 2019, pp. 724–29. Pubmed, doi:10.1182/blood-2018-07-862946.
Qian M, Xu H, Perez-Andreu V, Roberts KG, Zhang H, Yang W, Zhang S, Zhao X, Smith C, Devidas M, Gastier-Foster JM, Raetz E, Larsen E, Burchard EG, Winick N, Bowman WP, Martin PL, Borowitz M, Wood B, Antillon-Klussmann F, Pui C-H, Mullighan CG, Evans WE, Hunger SP, Relling MV, Loh ML, Yang JJ. Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanics. Blood. 2019 Feb 14;133(7):724–729.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

February 14, 2019

Volume

133

Issue

7

Start / End Page

724 / 729

Location

United States

Related Subject Headings

  • Transcriptional Regulator ERG
  • Prognosis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Polymorphism, Single Nucleotide
  • Oncogene Proteins, Fusion
  • Male
  • Immunology
  • Humans
  • Hispanic or Latino
  • Genotype