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Germline genomic variants associated with childhood acute lymphoblastic leukemia

2009; Nature Portfolio; Volume: 41; Issue: 9 Linguagem: Inglês

10.1038/ng.432

1546-1718

Lisa R. Treviño, Wenjian Yang, Deborah French, Stephen P. Hunger, William L. Carroll, Meenakshi Devidas, Cheryl L. Willman, Geoffrey Neale, James R. Downing, Susana C. Raimondi, Ching‐Hon Pui, William E. Evans, Mary V. Relling,

Childhood Cancer Survivors' Quality of Life

Mary Relling and colleagues report results of a genome-wide association study of childhood acute lymphoblastic leukemia (ALL) and its subtypes, identifying a specific association between common variants in ARID5B and B-hyperdiploid ALL. Using the Affymetrix 500K Mapping array and publicly available genotypes, we identified 18 SNPs whose allele frequency differed significantly(P < 1 × 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 × 10−15, odds ratio (OR) = 1.91; rs10994982, P = 5.7 × 10−9, OR = 1.62) but also distinguished B-hyperdiploid ALL from other subtypes (rs10821936, P = 1.62 × 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.