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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2018.00570

A genome-wide study of allele-specific expression in colorectal cancer.

 Xiao Dong1*, Zhi Liu2 and Yixue Li3
  • 1Albert Einstein College of Medicine, United States
  • 2Nanjing Medical University, China
  • 3Partner Institute for Computational Biology, China

Accumulating evidence from small-scale studies has suggested that allele-specific expression (ASE) plays important roles in tumor initiation and progression. However, few 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 ASE of single nucleotide variations (SNVs) from tumor and normal tissues of 59 individuals with CRC. We observed Increased ASE level in tumor samples, and the ASEs enrich as hotspots on the genome, 63% of the genes located there were previously reported to be with complex regulatory elements, e.g., human leukocyte antigen (HLA), or implicated in tumor progression. Further focusing 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 are possibly contributed by 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 tumor and normal tissues, and will be of critical value in guiding ASE studies in cancer.

Keywords: allele-specific expression, colorectal cancer, Cis-regulatory variation, somatic mutation, tumor

Received: 19 Jul 2018; Accepted: 06 Nov 2018.

Edited by:

Chuan Lu, Aberystwyth University, United Kingdom

Reviewed by:

Younghee Lee, School of Medicine, University of Utah, United States
Shihao Shen, University of California, Los Angeles, United States
Yanfeng Zhang, HudsonAlpha Institute for Biotechnology, United States  

Copyright: © 2018 Dong, Liu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Xiao Dong, Albert Einstein College of Medicine, New York City, United States, biosinodx@gmail.com