A high-dimensional, deep-sequencing study of lung adenocarcinoma in female never-smokers

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Title
A high-dimensional, deep-sequencing study of lung adenocarcinoma in female never-smokers
Author(s)
Sang Cheol Kim; Y Jung; jinah Park; S Cho; Chaehwa Seo; J Kim; P Kim; J Park; Jihae Seo; Jiwoong Kim; Seongjin ParkInsu Jang; Namshin Kim; Jin Ok YangByungUk Lee; K Rho; Y Jung; J Keum; J Lee; J Han; S Kang; S Bae; S J Choi; S Kim; J E Lee; W Kim; J Kim; Sanghyuk Lee
Bibliographic Citation
PLoS One, vol. 8, no. 2, pp. e55596-e55596
Publication Year
2013
Abstract
Background: Deep sequencing techniques provide a remarkable opportunity for comprehensive understanding of tumorigenesis at the molecular level. As omics studies become popular, integrative approaches need to be developed to move from a simple cataloguing of mutations and changes in gene expression to dissecting the molecular nature of carcinogenesis at the systemic level and understanding the complex networks that lead to cancer development. Results: Here, we describe a high-throughput, multi-dimensional sequencing study of primary lung adenocarcinoma tumors and adjacent normal tissues of six Korean female never-smoker patients. Our data encompass results from exome-seq, RNA-seq, small RNA-seq, and MeDIP-seq. We identified and validated novel genetic aberrations, including 47 somatic mutations and 19 fusion transcripts. One of the fusions involves the c-RET gene, which was recently reported to form fusion genes that may function as drivers of carcinogenesis in lung cancer patients. We also characterized gene expression profiles, which we integrated with genomic aberrations and gene regulations into functional networks. The most prominent gene network module that emerged indicates that disturbances in G2/M transition and mitotic progression are causally linked to tumorigenesis in these patients. Also, results from the analysis strongly suggest that several novel microRNA-target interactions represent key regulatory elements of the gene network. Conclusions: Our study not only provides an overview of the alterations occurring in lung adenocarcinoma at multiple levels from genome to transcriptome and epigenome, but also offers a model for integrative genomics analysis and proposes potential target pathways for the control of lung adenocarcinoma.
ISSN
1932-6203
Publisher
Public Library of Science
DOI
http://dx.doi.org/10.1371/journal.pone.0055596
Type
Article
Appears in Collections:
Korea Bioinformation Center > 1. Journal Articles
Synthetic Biology and Bioengineering Research Institute > Genome Editing Research Center > 1. Journal Articles
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