Large-scale profiling and identification of potential regulatory mechanisms for allelic gene expression in colorectal cancer cells

• Published in: Gene Vol. 512; no. 1; pp. 16 - 22
• Main Authors: Lee, Robin Dong-Woo, Song, Min-Young, Lee, Jong-Keuk
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2013
• Subjects: Alelic gene expression; Allele substitution; Alleles; Allelic Imbalance; B-lymphocytes; B-Lymphocytes - metabolism; Carcinoma - genetics; Cell Line, Tumor; Colorectal cancer; Colorectal cancer cells; colorectal neoplasms; Colorectal Neoplasms - genetics; Data processing; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genotype; Humans; Lymphocytes B; Monoallelic expression; phenotypic variation; Polymorphism, Single Nucleotide; promoter regions; Promoter Regions, Genetic; Promoters; RNA editing; Single nucleotide polymorphism (SNP); Single-nucleotide polymorphism; Tumor cell lines; MAE; Colorectal cancer cells; Allelic imbalance; SNP; Allele substitution; CEPH; AI; Alelic gene expression; ADAR; eQTL; Single nucleotide polymorphism (SNP); Monoallelic expression
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2012.10.001

Allelic variation in gene expression is common in humans and this variation is associated with phenotypic variation. In this study, we employed high-density single nucleotide polymorphism (SNP) chips containing 13,900 exonic SNPs to identify genes with allelic gene expression in cells from colorectal cancer cell lines. We found 2 monoallelically expressed genes (ERAP2 and MYLK4), 32 genes with an allelic imbalance in their expression, and 13 genes showing allele substitution by RNA editing. Among a total of 34 allelically expressed genes in colorectal cancer cells, 15 genes (44.1%) were associated with cis-acting eQTL, indicating that large portions of allelically expressed genes are regulated by cis-acting mechanisms of gene expression. In addition, potential regulatory variants present in the proximal promoter regions of genes showing either monoallelic expression or allelic imbalance were not tightly linked with coding SNPs, which were detected with allelic gene expression. These results suggest that multiple rare variants could be involved in the cis-acting regulatory mechanism of allelic gene expression. In the comparison with allelic gene expression data from Centre d'Etude du Polymorphisme Humain (CEPH) family B cells, 12 genes showed B-cell specific allelic imbalance and 1 noncoding SNP showed colorectal cancer cell-specific allelic imbalance. In addition, different patterns of allele substitution were observed between B cells and colorectal cancer cells. Overall, our study not only indicates that allelic gene expression is common in colorectal cancer cells, but our study also provides a better understanding of allele-specific gene expression in colorectal cancer cells. ► Allelic gene expression was identified in colorectal cancer cells using SNP chip. ► We detected monoallelic gene expression, allelic imbalance and allele substitution. ► Allelic gene expression is common in colorectal cancer cells.