title: Systematic identification of genes with a cancer-testis expression pattern in 19 cancer types.
abstract: Cancer-testis (CT) genes represent the similarity between the processes of spermatogenesis and tumorigenesis. It is possible that their selective expression pattern can help identify driver genes in cancer. In this study, we integrate transcriptomics data from multiple databases and systematically identify 876 new CT genes in 19 cancer types. We explore their relationship with testis-specific regulatory elements. We propose that extremely highly expressed CT genes (EECTGs) are potential drivers activated through epigenetic mechanisms. We find mutually exclusive associations between EECTGs and somatic mutations in mutated genes, such as PIK3CA in breast cancer. We also provide evidence that promoter demethylation and close non-coding RNAs (namely, CT-ncRNAs) may be two mechanisms to reactivate EECTG gene expression. We show that the meiosis-related EECTG (MEIOB) and its nearby CT-ncRNA have a role in tumorigenesis in lung adenocarcinoma. Our findings provide methods for identifying epigenetic-driver genes of cancer, which could serve as targets of future cancer therapies.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Kaipeng
authors.initials: K
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Ningbin
authors.initials: N
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xuejiang
authors.identifier: http://orcid.org/0000-0002-0475-5705
authors.initials: X
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Mingxi
authors.initials: M
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Bioinformatics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Linxiang
authors.initials: L
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention &Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Digestive Endoscopy Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention &Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Shouyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Huo
authors.affiliation: Department of Bioinformatics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Qianghu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Molecular and Cellular Oncology, Cancer Biology Program, Center for RNA Interference and Non-Coding RNAs, the University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Yang
authors.affiliation: School of Life Science and Technology, Shanghai Tech University, 100 Haike Road, Pudong New Area, Shanghai 201210, China.
authors.forename: Xingxu
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department 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 210029, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D005810:Multigene Family; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: D000951:Antigens, Neoplasm
references.citation: Nat Rev Genet. 2009 Jan;10(1):57-63
references.pmid: 19015660
references.citation: Cancer Discov. 2015 May;5(5):488-505
references.pmid: 25770156
references.citation: Nat Commun. 2013;4:2788
references.pmid: 24240703
references.citation: Cell. 2011 Mar 18;144(6):864-73
references.pmid: 21414479
references.citation: Science. 2015 May 8;348(6235):666-9
references.pmid: 25954003
references.citation: Cancer Res. 2010 Jul 15;70(14):5829-39
references.pmid: 20587513
references.citation: Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):118-23
references.pmid: 25535351
references.citation: Mol Oncol. 2011 Apr;5(2):164-82
references.pmid: 21376678
references.citation: Bioinformatics. 2014 Sep 1;30(17):2480-5
references.pmid: 24813212
references.citation: Cell. 2011 Nov 23;147(5):1066-79
references.pmid: 22118463
references.citation: Nat Genet. 2009 Jul;41(7):843-8
references.pmid: 19483683
references.citation: Science. 2015 May 8;348(6235):660-5
references.pmid: 25954002
references.citation: Genes Dev. 2013 Oct 15;27(20):2233-45
references.pmid: 24142874
references.citation: Cancer Res. 1999 Jul 1;59(13):3157-65
references.pmid: 10397259
references.citation: Nature. 2014 Jan 23;505(7484):495-501
references.pmid: 24390350
references.citation: J Immunother Emphasis Tumor Immunol. 1993 Aug;14(2):104-9
references.pmid: 8280701
references.citation: Oncoimmunology. 2013 Aug 1;2(8):e26012
references.pmid: 24083085
references.citation: Int J Biochem Cell Biol. 2013 May;45(5):973-8
references.pmid: 23420006
references.citation: Annu Rev Pharmacol Toxicol. 2014;54:251-72
references.pmid: 24160706
references.citation: EMBO Mol Med. 2013 Feb;5(2):169-72
references.pmid: 23339072
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20422-7
references.pmid: 19088187
references.citation: Nature. 2014 Sep 11;513(7517):202-9
references.pmid: 25079317
references.citation: Nat Rev Genet. 2013 Nov;14(11):794-806
references.pmid: 24136506
references.citation: Nat Genet. 2015 Mar;47(3):199-208
references.pmid: 25599403
references.citation: Nat Genet. 2012 Nov;44(11):1199-206
references.pmid: 23042116
references.citation: Cancer Res. 2014 Sep 1;74(17):4694-705
references.pmid: 24970476
references.citation: Cell. 2015 Feb 12;160(4):715-28
references.pmid: 25679763
references.citation: Nat Rev Cancer. 2012 Apr;12(4):237-51
references.pmid: 22437869
references.citation: Trends Pharmacol Sci. 2014 Jan;35(1):41-50
references.pmid: 24361003
references.citation: Cell. 2012 Aug 17;150(4):673-84
references.pmid: 22901802
references.citation: J Clin Oncol. 2013 Jul 1;31(19):2396-403
references.pmid: 23715567
references.citation: Nat Rev Cancer. 2005 Aug;5(8):615-25
references.pmid: 16034368
references.citation: Nature. 2014 Jul 31;511(7511):543-50
references.pmid: 25079552
references.citation: Nature. 2012 Oct 4;490(7418):61-70
references.pmid: 23000897
references.citation: Nature. 2013 Oct 17;502(7471):333-9
references.pmid: 24132290
references.citation: Nature. 2013 May 2;497(7447):67-73
references.pmid: 23636398
references.citation: Immunity. 1995 Feb;2(2):167-75
references.pmid: 7895173
references.citation: Nat Genet. 2013 Oct;45(10):1113-20
references.pmid: 24071849
references.citation: Eur J Hum Genet. 2009 Nov;17(11):1463-70
references.pmid: 19471314
references.citation: Science. 2013 Mar 29;339(6127):1546-58
references.pmid: 23539594
references.citation: Nat Protoc. 2009;4(1):44-57
references.pmid: 19131956
references.citation: Science. 2014 Apr 11;344(6180):189-93
references.pmid: 24652939
references.citation: Nat Methods. 2014 Nov;11(11):1138-40
references.pmid: 25262207
references.citation: Cancer Cell. 2010 Jan 19;17(1):98-110
references.pmid: 20129251
references.citation: BMC Bioinformatics. 2010;11:94
references.pmid: 20167110
references.citation: Nature. 2014 May 29;509(7502):575-81
references.pmid: 24870542
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D816-9
references.pmid: 18838390
references.citation: J Clin Oncol. 2013 Jul 1;31(19):2388-95
references.pmid: 23715562
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16910-5
references.pmid: 20837533
references.citation: Science. 2015 May 8;348(6235):648-60
references.pmid: 25954001