Germline genomic variants associated with childhood acute lymphoblastic leukemia
Copyright policy )Germline genomic variants associated with childhood acute lymphoblastic leukemia
Using the Affymetrix 500K Mapping array and publicly available genotypes, we identified 18 SNPs whose allele frequency differed significantly(P < 1 x 10(-5)) between pediatric acute lymphoblastic leukemia (ALL) cases (n = 317) and non-ALL controls (n = 17,958). Two SNPs in ARID5B not only differed between ALL and non-ALL groups (rs10821936, P = 1.4 x 10(-15), odds ratio (OR) = 1.91; rs10994982, P = 5.7 x 10(-9), OR = 1.62) but also distinguished B-hyperdiploid ALL from other subtypes (rs10821936, P = 1.62 x 10(-5), OR = 2.17; rs10994982, P = 0.003, OR 1.72). These ARID5B SNPs also distinguished B-hyperdiploid ALL from other subtypes in an independent validation cohort (n = 124 children with ALL; P = 0.003 and P = 0.0008, OR 2.45 and 2.86, respectively) and were associated with methotrexate accumulation and gene expression pattern in leukemic lymphoblasts. We conclude that germline variants affect susceptibility to, and characteristics of, specific ALL subtypes.
- University of Colorado System United States
- New York University United States
- University of New Mexico United States
- University of Florida United States
- University of Colorado Denver United States
Antimetabolites, Antineoplastic, Chromosomes, Human, Pair 10, Gene Dosage, Genetic Variation, Cohort Studies, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Germ Cells, Gene Frequency, Haplotypes, Case-Control Studies, Child, Preschool, Dopa Decarboxylase, Humans, Genetic Predisposition to Disease, Child, Alleles, Chromosomes, Human, Pair 7, Germ-Line Mutation, Genome-Wide Association Study
Antimetabolites, Antineoplastic, Chromosomes, Human, Pair 10, Gene Dosage, Genetic Variation, Cohort Studies, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Germ Cells, Gene Frequency, Haplotypes, Case-Control Studies, Child, Preschool, Dopa Decarboxylase, Humans, Genetic Predisposition to Disease, Child, Alleles, Chromosomes, Human, Pair 7, Germ-Line Mutation, Genome-Wide Association Study
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