title: A high-dimensional, deep-sequencing study of lung adenocarcinoma in female never-smokers.
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.
authors: Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors: Sang Cheol
authors: SC
authors: Kim
authors: Yeonjoo
authors: Y
authors: Jung
authors: Jinah
authors: J
authors: Park
authors: Sooyoung
authors: S
authors: Cho
authors: Chaehwa
authors: C
authors: Seo
authors: Jaesang
authors: J
authors: Kim
authors: Pora
authors: P
authors: Kim
authors: Jehwan
authors: J
authors: Park
authors: Jihae
authors: J
authors: Seo
authors: Jiwoong
authors: J
authors: Kim
authors: Seongjin
authors: S
authors: Park
authors: Insu
authors: I
authors: Jang
authors: Namshin
authors: N
authors: Kim
authors: Jin Ok
authors: JO
authors: Yang
authors: Byungwook
authors: B
authors: Lee
authors: Kyoohyoung
authors: K
authors: Rho
authors: Yeonhwa
authors: Y
authors: Jung
authors: Juhee
authors: J
authors: Keum
authors: Jinseon
authors: J
authors: Lee
authors: Jungho
authors: J
authors: Han
authors: Sangeun
authors: S
authors: Kang
authors: Sujin
authors: S
authors: Bae
authors: So-Jung
authors: SJ
authors: Choi
authors: Sujin
authors: S
authors: Kim
authors: Jong-Eun
authors: JE
authors: Lee
authors: Wankyu
authors: W
authors: Kim
authors: Jhingook
authors: J
authors: Kim
authors: Sanghyuk
authors: S
authors: Lee
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger