A Genome-Wide Study of Allele-Specific Expression in Colorectal Cancer
Accumulating evidence from small-scale studies has suggested that allele-specific expression (ASE) plays an important role in tumor initiation and progression. However, little is known about genome-wide ASE in tumors. In this study, we conducted a comprehensive analysis of ASE in individuals with co...
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doaj-40a7cb741ea54d90bf1d05d56ca5b8e72020-11-25T00:37:30ZengFrontiers Media S.A.Frontiers in Genetics1664-80212018-11-01910.3389/fgene.2018.00570414764A Genome-Wide Study of Allele-Specific Expression in Colorectal CancerZhi Liu0Xiao Dong1Yixue Li2Yixue Li3Yixue Li4Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, United StatesKey Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaShanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai, ChinaCollaborative Innovation Center for Genetics and Development, Fudan University, Shanghai, ChinaAccumulating evidence from small-scale studies has suggested that allele-specific expression (ASE) plays an important role in tumor initiation and progression. However, little is known about genome-wide ASE in tumors. In this study, we conducted a comprehensive analysis of ASE in individuals with colorectal cancer (CRC) on a genome-wide scale. We identified 5.4 thousand genome-wide ASEs of single nucleotide variations (SNVs) from tumor and normal tissues of 59 individuals with CRC. We observed an increased ASE level in tumor samples and the ASEs enriched as hotspots on the genome. Around 63% of the genes located there were previously reported to contain complex regulatory elements, e.g., human leukocyte antigen (HLA), or were implicated in tumor progression. Focussing on the allelic expression of somatic mutations, we found that 37.5% of them exhibited ASE, and genes harboring such somatic mutations, were enriched in important pathways implicated in cancers. In addition, by comparing the expected and observed ASE events in tumor samples, we identified 50 tumor specific ASEs which possibly contributed to the somatic events in the regulatory regions of the genes and significantly enriched known cancer driver genes. By analyzing CRC ASEs from several perspectives, we provided a systematic understanding of how ASE is implicated in both tumor and normal tissues and will be of critical value in guiding ASE studies in cancer.https://www.frontiersin.org/article/10.3389/fgene.2018.00570/fullallele-specific expressioncolorectal cancercis-regulatory variationsomatic mutationtumor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhi Liu Xiao Dong Yixue Li Yixue Li Yixue Li |
spellingShingle |
Zhi Liu Xiao Dong Yixue Li Yixue Li Yixue Li A Genome-Wide Study of Allele-Specific Expression in Colorectal Cancer Frontiers in Genetics allele-specific expression colorectal cancer cis-regulatory variation somatic mutation tumor |
author_facet |
Zhi Liu Xiao Dong Yixue Li Yixue Li Yixue Li |
author_sort |
Zhi Liu |
title |
A Genome-Wide Study of Allele-Specific Expression in Colorectal Cancer |
title_short |
A Genome-Wide Study of Allele-Specific Expression in Colorectal Cancer |
title_full |
A Genome-Wide Study of Allele-Specific Expression in Colorectal Cancer |
title_fullStr |
A Genome-Wide Study of Allele-Specific Expression in Colorectal Cancer |
title_full_unstemmed |
A Genome-Wide Study of Allele-Specific Expression in Colorectal Cancer |
title_sort |
genome-wide study of allele-specific expression in colorectal cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2018-11-01 |
description |
Accumulating evidence from small-scale studies has suggested that allele-specific expression (ASE) plays an important role in tumor initiation and progression. However, little is known about genome-wide ASE in tumors. In this study, we conducted a comprehensive analysis of ASE in individuals with colorectal cancer (CRC) on a genome-wide scale. We identified 5.4 thousand genome-wide ASEs of single nucleotide variations (SNVs) from tumor and normal tissues of 59 individuals with CRC. We observed an increased ASE level in tumor samples and the ASEs enriched as hotspots on the genome. Around 63% of the genes located there were previously reported to contain complex regulatory elements, e.g., human leukocyte antigen (HLA), or were implicated in tumor progression. Focussing on the allelic expression of somatic mutations, we found that 37.5% of them exhibited ASE, and genes harboring such somatic mutations, were enriched in important pathways implicated in cancers. In addition, by comparing the expected and observed ASE events in tumor samples, we identified 50 tumor specific ASEs which possibly contributed to the somatic events in the regulatory regions of the genes and significantly enriched known cancer driver genes. By analyzing CRC ASEs from several perspectives, we provided a systematic understanding of how ASE is implicated in both tumor and normal tissues and will be of critical value in guiding ASE studies in cancer. |
topic |
allele-specific expression colorectal cancer cis-regulatory variation somatic mutation tumor |
url |
https://www.frontiersin.org/article/10.3389/fgene.2018.00570/full |
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