concordant gene expression in leukemia cells and normal leukocytes is associated with germline cis-snps整合基因表达在白血病细胞和正常白细胞与生殖系cis-snps相关联.pdf

Concordant Gene Expression in Leukemia Cells and Normal Leukocytes Is Associated with Germline cis-SNPs 1 1 1 2 2 3 Deborah French , Wenjian Yang , Leo H. Hamilton , Geoffrey Neale , Yiping Fan , James R. Downing , Nancy J. Cox6, Ching-Hon Pui4,5, William E. Evans1,5, Mary V. Relling1,5* 1 Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America, 2 Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America, 3 Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America, 4 Department of Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America, 5 University of Tennessee, Memphis, Tennessee, United States of America, 6 Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America Abstract The degree to which gene expression covaries between different primary tissues within an individual is not well defined. We hypothesized that expression that is concordant across tissues is more likely influenced by genetic variability than gene expression which is discordant between tissues. We quantified expression of 11,873 genes in paired samples of primary leukemia cells and normal leukocytes from 92 patients with acute lymphoblastic leukemia (ALL). Genetic variation at .500,000 single nucleotide polymorphisms (SNPs) was also assessed. The expression of only 176/11,783 (1.5%) genes was correlated (p,0.008, FDR = 25%) in the two tissue types, but expression of a high proportion (20 of these 176 genes) was significantly related to cis-SNP genotypes (adjusted p,0.05). In an