Treviño Lisa R, Yang Wenjian, French Deborah, Hunger Stephen P, Carroll William L, Devidas Meenakshi, Willman Cheryl, Neale Geoffrey, Downing James, Raimondi Susana C, Pui Ching-Hon, Evans William E, Relling Mary V
St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Nat Genet. 2009 Sep;41(9):1001-5. doi: 10.1038/ng.432. Epub 2009 Aug 16.
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.
利用Affymetrix 500K基因分型芯片和公开可得的基因型数据，我们在小儿急性淋巴细胞白血病（ALL）病例（n = 317）和非ALL对照（n = 17,958）中鉴定出18个单核苷酸多态性（SNP），其等位基因频率存在显著差异（P < 1 × 10⁻⁵）。ARID5B基因中的两个SNP不仅在ALL组和非ALL组之间存在差异（rs10821936，P = 1.4 × 10⁻¹⁵，优势比（OR） = 1.91；rs10994982，P = 5.7 × 10⁻⁹，OR = 1.62），还能区分B-超二倍体ALL与其他亚型（rs10821936，P = 1.62 × 10⁻⁵，OR = 2.17；rs10994982，P = 0.003，OR = 1.72）。在一个独立验证队列（n = 124例ALL患儿）中，这些ARID5B基因的SNP同样能区分B-超二倍体ALL与其他亚型（P = 0.003和P = 0.0008，OR分别为2.45和2.86），并且与白血病淋巴母细胞中甲氨蝶呤的蓄积及基因表达模式相关。我们得出结论，种系变异影响特定ALL亚型的易感性及其特征。
