Germline genomic variants associated with childhood acute lymphoblastic leukemia

被引：376

作者：

Trevino, Lisa R. ^{[1
]}

Yang, Wenjian ^{[1
]}

French, Deborah ^{[1
]}

Hunger, Stephen P. ^{[2
]}

Carroll, William L. ^{[3
]}

Devidas, Meenakshi ^{[4
]}

Willman, Cheryl ^{[5
]}

Neale, Geoffrey ^{[1
]}

Downing, James ^{[1
]}

Raimondi, Susana C. ^{[1
]}

Pui, Ching-Hon ^{[1
]}

Evans, William E. ^{[1
]}

Relling, Mary V. ^{[1
]}

机构：

[1] St Jude Childrens Res Hosp, Memphis, TN 38105 USA

[2] Univ Colorado, Denver, CO 80202 USA

[3] NYU, Med Ctr, New York, NY 10016 USA

[4] Univ Florida, Gainesville, FL USA

[5] Univ New Mexico, Albuquerque, NM 87131 USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 09期

基金：

英国惠康基金;

关键词：

METHYLENETETRAHYDROFOLATE REDUCTASE MTHFR; MINIMAL RESIDUAL DISEASE; DNA-BINDING PROPERTIES; IKAROS GENE ENCODES; NATIONAL-INSTITUTE; BIPOLAR DISORDER; WIDE ANALYSIS; IN-VIVO; POLYMORPHISMS; EXPRESSION;

D O I：

10.1038/ng.432

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1001 / U67

页数：7

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