Comprehensive Genomic Characterization of Long Non-coding RNAs across Human Cancers

Xiaohui Yan; Zhongyi Hu; Yi Feng; Xiaowen Hu; Jiao Yuan; Sihai D Zhao; Youyou Zhang; Lu Yang; Weiwei Shan; Qun He; Lingling Fan; Lana E Kandalaft; Janos L Tanyi; Chunsheng Li; Chao-Xing Yuan; Dongmei Zhang; Huiqing Yuan; Keqin Hua; Yiling Lu; Dionyssios Katsaros; Qihong Huang; Kathleen Montone; Yi Fan; George Coukos; Jeff Boyd; Anil K Sood; Timothy Rebbeck; Gordon B Mills; Chi V Dang; Lin Zhang

doi:10.1016/j.ccell.2015.09.006

Comprehensive Genomic Characterization of Long Non-coding RNAs across Human Cancers

Cancer Cell. 2015 Oct 12;28(4):529-540. doi: 10.1016/j.ccell.2015.09.006.

Authors

Xiaohui Yan¹, Zhongyi Hu², Yi Feng³, Xiaowen Hu², Jiao Yuan², Sihai D Zhao⁴, Youyou Zhang², Lu Yang⁵, Weiwei Shan¹, Qun He², Lingling Fan¹, Lana E Kandalaft⁶, Janos L Tanyi⁷, Chunsheng Li⁸, Chao-Xing Yuan⁹, Dongmei Zhang⁵, Huiqing Yuan¹⁰, Keqin Hua¹¹, Yiling Lu¹², Dionyssios Katsaros¹³, Qihong Huang¹⁴, Kathleen Montone¹⁵, Yi Fan¹⁶, George Coukos¹⁷, Jeff Boyd¹⁸, Anil K Sood¹⁹, Timothy Rebbeck²⁰, Gordon B Mills¹², Chi V Dang²¹, Lin Zhang²²

Affiliations

¹ Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
² Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
³ Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁴ Department of Statistics, University of Illinois at Urbana-Champaign, Champaign, IL 61820, USA.
⁵ Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; West China Medical School, Sichuan University, Chengdu 610041, China.
⁶ Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Ludwig Center for Cancer Research and Department of Oncology, University of Lausanne, Lausanne 1007, Switzerland.
⁷ Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁸ Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁹ Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁰ Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan 250012, China.
¹¹ Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
¹² Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
¹³ Department of Surgical Sciences, Gynecologic Oncology, Azienda Ospedaliero - Universitaria Citta della Salute, Turin 10126, Italy.
¹⁴ Wistar Institute, Philadelphia, PA 19104, USA.
¹⁵ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁶ Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁷ Ludwig Center for Cancer Research and Department of Oncology, University of Lausanne, Lausanne 1007, Switzerland.
¹⁸ Cancer Genome Institute, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.
¹⁹ Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
²⁰ Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
²¹ Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: dangvchi@exchange.upenn.edu.
²² Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: linzhang@mail.med.upenn.edu.

Abstract

The discovery of long non-coding RNA (lncRNA) has dramatically altered our understanding of cancer. Here, we describe a comprehensive analysis of lncRNA alterations at transcriptional, genomic, and epigenetic levels in 5,037 human tumor specimens across 13 cancer types from The Cancer Genome Atlas. Our results suggest that the expression and dysregulation of lncRNAs are highly cancer type specific compared with protein-coding genes. Using the integrative data generated by this analysis, we present a clinically guided small interfering RNA screening strategy and a co-expression analysis approach to identify cancer driver lncRNAs and predict their functions. This provides a resource for investigating lncRNAs in cancer and lays the groundwork for the development of new diagnostics and treatments.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Computational Biology / methods
Epigenesis, Genetic
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Genetic Variation*
Genome, Human
Humans
Neoplasms / genetics*
RNA, Long Noncoding / genetics*
Transcription, Genetic

Substances

RNA, Long Noncoding

Abstract

Publication types

MeSH terms

Substances

Grants and funding