Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, University of Montreal, Montreal, QC H3T 1C5, Canada.
Department of Pharmacology, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada.
Pharmacogenomics. 2019 Nov;20(17):1189-1197. doi: 10.2217/pgs-2019-0087. Epub 2019 Nov 5.
To evaluate top-ranking genes identified through genome-wide association studies for an association with corticosteroid-related osteonecrosis in children with acute lymphoblastic leukemia (ALL) who received Dana-Farber Cancer Institute treatment protocols. Lead SNPs from these studies, as well as other variants in the same genes, pooled from whole exome sequencing data, were analyzed for an association with osteonecrosis in childhood ALL patients from Quebec cohort. Top-ranking variants were verified in the replication patient group. The analyses of variants in the locus derived from whole exome sequencing data showed an association of several correlated SNPs (rs11553746, rs2290911, rs7595075, rs2306060 and rs79716074). The rs79716074 defines *B haplotype of the gene, which is well known for its functional role. This study confirms implication of the gene in the treatment-related osteonecrosis in childhood ALL and identifies novel, potentially causal variant of this complication.
评估通过全基因组关联研究确定的与接受达纳-法伯癌症研究所治疗方案的儿童急性淋巴细胞白血病 (ALL) 患者皮质类固醇相关骨坏死相关的顶级基因。 从这些研究中提取的主要单核苷酸多态性 (SNP) 以及来自全外显子组测序数据的同一基因中的其他变体，用于分析魁北克队列中儿童 ALL 患者的骨坏死相关性。在验证患者组中验证了排名靠前的变体。 全外显子组测序数据衍生的 基因座变体分析显示，几个相关 SNP(rs11553746、rs2290911、rs7595075、rs2306060 和 rs79716074) 存在关联。rs79716074 定义了 基因的 *B 单倍型，该单倍型以其功能作用而闻名。 本研究证实了 基因在儿童 ALL 治疗相关骨坏死中的作用，并确定了这种并发症的新的、潜在的因果变体。
