Exploring the effects of genetic variation on gene regulation in cancer in the context of 3D genome structure
Tóm tắt
Numerous genome-wide association studies (GWAS) conducted to date revealed genetic variants associated with various diseases, including breast and prostate cancers. Despite the availability of these large-scale data, relatively few variants have been functionally characterized, mainly because the majority of single-nucleotide polymorphisms (SNPs) map to the non-coding regions of the human genome. The functional characterization of these non-coding variants and the identification of their target genes remain challenging. In this communication, we explore the potential functional mechanisms of non-coding SNPs by integrating GWAS with the high-resolution chromosome conformation capture (Hi-C) data for breast and prostate cancers. We show that more genetic variants map to regulatory elements through the 3D genome structure than the 1D linear genome lacking physical chromatin interactions. Importantly, the association of enhancers, transcription factors, and their target genes with breast and prostate cancers tends to be higher when these regulatory elements are mapped to high-risk SNPs through spatial interactions compared to simply using a linear proximity. Finally, we demonstrate that topologically associating domains (TADs) carrying high-risk SNPs also contain gene regulatory elements whose association with cancer is generally higher than those belonging to control TADs containing no high-risk variants. Our results suggest that many SNPs may contribute to the cancer development by affecting the expression of certain tumor-related genes through long-range chromatin interactions with gene regulatory elements. Integrating large-scale genetic datasets with the 3D genome structure offers an attractive and unique approach to systematically investigate the functional mechanisms of genetic variants in disease risk and progression.
Tài liệu tham khảo
citation_journal_title=Cancer Cell Int; citation_title=From ‘omics’ to complex disease: a systems biology approach to gene-environment interactions in cancer; citation_author=SS Knox; citation_volume=10; citation_publication_date=2010; citation_pages=11; citation_doi=10.1186/1475-2867-10-11; citation_id=CR1
citation_journal_title=J Thorac Dis; citation_title=Cancer prevention from the perspective of global cancer burden patterns; citation_author=H Nagai, YH Kim; citation_volume=9; citation_issue=3; citation_publication_date=2017; citation_pages=448-451; citation_doi=10.21037/jtd.2017.02.75; citation_id=CR2
citation_journal_title=Nat Med; citation_title=Cancer genes and the pathways they control; citation_author=B Vogelstein, KW Kinzler; citation_volume=10; citation_issue=8; citation_publication_date=2004; citation_pages=789-799; citation_doi=10.1038/nm1087; citation_id=CR3
citation_journal_title=BMC Genomics; citation_title=Oncogenes and tumor suppressor genes: comparative genomics and network perspectives; citation_author=K Zhu; citation_volume=16; citation_issue=Suppl 7; citation_publication_date=2015; citation_pages=S8; citation_doi=10.1186/1471-2164-16-S7-S8; citation_id=CR4
citation_journal_title=Trends Genet; citation_title=Chromatin interactions and regulatory elements in cancer: from bench to bedside; citation_author=YX See, BZ Wang, MJ Fullwood; citation_volume=35; citation_issue=2; citation_publication_date=2019; citation_pages=145-158; citation_doi=10.1016/j.tig.2018.11.007; citation_id=CR5
Flavahan WA, Gaskell E, Bernstein BE. Epigenetic plasticity and the hallmarks of cancer. Science. 2017;357(6348):eaal2380.
citation_journal_title=World J Oncol; citation_title=Epidemiology of prostate cancer; citation_author=P Rawla; citation_volume=10; citation_issue=2; citation_publication_date=2019; citation_pages=63-89; citation_doi=10.14740/wjon1191; citation_id=CR7
citation_journal_title=Breast Cancer; citation_title=Breast cancer incidence, mortality and mortality-to-incidence ratio (MIR) are associated with human development, 1990-2016: evidence from global burden of disease study 2016; citation_author=R Sharma; citation_volume=26; citation_issue=4; citation_publication_date=2019; citation_pages=428-445; citation_doi=10.1007/s12282-018-00941-4; citation_id=CR8
citation_journal_title=Breast Cancer Res; citation_title=Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer; citation_author=SA Eccles; citation_volume=15; citation_issue=5; citation_publication_date=2013; citation_pages=R92; citation_doi=10.1186/bcr3493; citation_id=CR9
citation_journal_title=J Hematol Oncol; citation_title=Recent advances of therapeutic targets based on the molecular signature in breast cancer: genetic mutations and implications for current treatment paradigms; citation_author=ZS Lima; citation_volume=12; citation_issue=1; citation_publication_date=2019; citation_pages=38; citation_doi=10.1186/s13045-019-0725-6; citation_id=CR10
citation_journal_title=Breast Cancer Res Treat; citation_title=Time to death in breast cancer patients as an indicator of treatment response; citation_author=SA Narod, V Giannakeas, V Sopik; citation_volume=172; citation_issue=3; citation_publication_date=2018; citation_pages=659-669; citation_doi=10.1007/s10549-018-4935-3; citation_id=CR11
citation_journal_title=Asia Pac J Public Health; citation_title=Risk factors of breast cancer: a systematic review and meta-analysis; citation_author=T Anothaisintawee; citation_volume=25; citation_issue=5; citation_publication_date=2013; citation_pages=368-387; citation_doi=10.1177/1010539513488795; citation_id=CR12
citation_journal_title=Nat Genet; citation_title=Polygenic susceptibility to breast cancer and implications for prevention; citation_author=PD Pharoah; citation_volume=31; citation_issue=1; citation_publication_date=2002; citation_pages=33-36; citation_doi=10.1038/ng853; citation_id=CR13
citation_journal_title=Int J Cancer; citation_title=Prevalence of incidental prostate cancer: a systematic review of autopsy studies; citation_author=KJ Bell; citation_volume=137; citation_issue=7; citation_publication_date=2015; citation_pages=1749-1757; citation_doi=10.1002/ijc.29538; citation_id=CR14
citation_journal_title=JAMA; citation_title=Familial risk and heritability of cancer among twins in Nordic countries; citation_author=LA Mucci; citation_volume=315; citation_issue=1; citation_publication_date=2016; citation_pages=68-76; citation_doi=10.1001/jama.2015.17703; citation_id=CR15
citation_journal_title=Nat Rev Cancer; citation_title=Genome-wide association studies of cancer: current insights and future perspectives; citation_author=A Sud, B Kinnersley, RS Houlston; citation_volume=17; citation_issue=11; citation_publication_date=2017; citation_pages=692-704; citation_doi=10.1038/nrc.2017.82; citation_id=CR16
citation_journal_title=Nat Commun; citation_title=Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes; citation_author=A Xue; citation_volume=9; citation_issue=1; citation_publication_date=2018; citation_pages=2941; citation_doi=10.1038/s41467-018-04951-w; citation_id=CR17
citation_journal_title=Alzheimers Res Ther; citation_title=Genome-wide analysis of genetic predisposition to Alzheimer's disease and related sex disparities; citation_author=A Nazarian, AI Yashin, AM Kulminski; citation_volume=11; citation_issue=1; citation_publication_date=2019; citation_pages=5; citation_doi=10.1186/s13195-018-0458-8; citation_id=CR18
citation_journal_title=Nat Rev Immunol; citation_title=The genetics and immunopathogenesis of inflammatory bowel disease; citation_author=JH Cho; citation_volume=8; citation_issue=6; citation_publication_date=2008; citation_pages=458-466; citation_doi=10.1038/nri2340; citation_id=CR19
citation_journal_title=Genome Biol; citation_title=Genetic disease risks can be misestimated across global populations; citation_author=MS Kim; citation_volume=19; citation_issue=1; citation_publication_date=2018; citation_pages=179; citation_doi=10.1186/s13059-018-1561-7; citation_id=CR20
citation_journal_title=Nat Rev Genet; citation_title=Benefits and limitations of genome-wide association studies; citation_author=V Tam; citation_volume=20; citation_issue=8; citation_publication_date=2019; citation_pages=467-484; citation_doi=10.1038/s41576-019-0127-1; citation_id=CR21
citation_journal_title=Nat Commun; citation_title=Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer; citation_author=AP Klein; citation_volume=9; citation_issue=1; citation_publication_date=2018; citation_pages=556; citation_doi=10.1038/s41467-018-02942-5; citation_id=CR22
citation_journal_title=PLoS One; citation_title=Genome-wide association study (GWAS) of ovarian cancer in Japanese predicted regulatory variants in 22q13.1; citation_author=V Yodsurang; citation_volume=13; citation_issue=12; citation_publication_date=2018; citation_doi=10.1371/journal.pone.0209096; citation_id=CR23
citation_journal_title=Nat Genet; citation_title=Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes; citation_author=JD McKay; citation_volume=49; citation_issue=7; citation_publication_date=2017; citation_pages=1126-1132; citation_doi=10.1038/ng.3892; citation_id=CR24
citation_journal_title=Cancer Epidemiol Biomarkers Prev; citation_title=A review of prostate cancer genome-wide association studies (GWAS); citation_author=S Benafif; citation_volume=27; citation_issue=8; citation_publication_date=2018; citation_pages=845-857; citation_doi=10.1158/1055-9965.EPI-16-1046; citation_id=CR25
citation_journal_title=Nat Commun; citation_title=Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer; citation_author=MA Ferreira; citation_volume=10; citation_issue=1; citation_publication_date=2019; citation_pages=1741; citation_doi=10.1038/s41467-018-08053-5; citation_id=CR26
citation_journal_title=Nat Commun; citation_title=Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants; citation_author=X Shu; citation_volume=11; citation_issue=1; citation_publication_date=2020; citation_pages=1217; citation_doi=10.1038/s41467-020-15046-w; citation_id=CR27
citation_journal_title=Nat Commun; citation_title=12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population; citation_author=R Takata; citation_volume=10; citation_issue=1; citation_publication_date=2019; citation_pages=4422; citation_doi=10.1038/s41467-019-12267-6; citation_id=CR28
citation_journal_title=Nature; citation_title=A map of human genome variation from population-scale sequencing; citation_author=GR Abecasis; citation_volume=467; citation_issue=7319; citation_publication_date=2010; citation_pages=1061-1073; citation_doi=10.1038/nature09534; citation_id=CR29
citation_journal_title=Biochim Biophys Acta; citation_title=Genetic variation in the non-coding genome: involvement of micro-RNAs and long non-coding RNAs in disease; citation_author=B Hrdlickova; citation_volume=1842; citation_issue=10; citation_publication_date=2014; citation_pages=1910-1922; citation_doi=10.1016/j.bbadis.2014.03.011; citation_id=CR30
citation_journal_title=Nucleic Acids Res; citation_title=A screen for deeply conserved non-coding GWAS SNPs uncovers a MIR-9-2 functional mutation associated to retinal vasculature defects in human; citation_author=R Madelaine; citation_volume=46; citation_issue=7; citation_publication_date=2018; citation_pages=3517-3531; citation_doi=10.1093/nar/gky166; citation_id=CR31
citation_journal_title=Nat Commun; citation_title=Functional genomics reveal gene regulatory mechanisms underlying schizophrenia risk; citation_author=Y Huo; citation_volume=10; citation_issue=1; citation_publication_date=2019; citation_pages=670; citation_doi=10.1038/s41467-019-08666-4; citation_id=CR32
citation_journal_title=Brief Bioinform; citation_title=Regulatory variants: from detection to predicting impact; citation_author=E Rojano; citation_volume=20; citation_issue=5; citation_publication_date=2019; citation_pages=1639-1654; citation_doi=10.1093/bib/bby039; citation_id=CR33
citation_journal_title=PLoS Genet; citation_title=regQTLs: single nucleotide polymorphisms that modulate microRNA regulation of gene expression in tumors; citation_author=G Wilk, R Braun; citation_volume=14; citation_issue=12; citation_publication_date=2018; citation_doi=10.1371/journal.pgen.1007837; citation_id=CR34
citation_journal_title=Brief Bioinform; citation_title=Exploring the function of genetic variants in the non-coding genomic regions: approaches for identifying human regulatory variants affecting gene expression; citation_author=MJ Li; citation_volume=16; citation_issue=3; citation_publication_date=2015; citation_pages=393-412; citation_doi=10.1093/bib/bbu018; citation_id=CR35
citation_journal_title=J Biol Chem; citation_title=Base substitution at position −88 in a beta-thalassemic globin gene. Further evidence for the role of distal promoter element ACACCC; citation_author=SH Orkin, SE Antonarakis, HH Kazazian; citation_volume=259; citation_publication_date=1984; citation_pages=8679-8681; citation_doi=10.1016/S0021-9258(17)47203-6; citation_id=CR36
citation_journal_title=Science; citation_title=TERT promoter mutations in familial and sporadic melanoma; citation_author=S Horn; citation_volume=339; citation_issue=6122; citation_publication_date=2013; citation_pages=959-961; citation_doi=10.1126/science.1230062; citation_id=CR37
citation_journal_title=Cell; citation_title=A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans; citation_author=GL Bond; citation_volume=119; citation_issue=5; citation_publication_date=2004; citation_pages=591-602; citation_doi=10.1016/j.cell.2004.11.022; citation_id=CR38
citation_journal_title=Nat Rev Genet; citation_title=Role of non-coding sequence variants in cancer; citation_author=E Khurana; citation_volume=17; citation_issue=2; citation_publication_date=2016; citation_pages=93-108; citation_doi=10.1038/nrg.2015.17; citation_id=CR39
citation_journal_title=Nat Genet; citation_title=High-throughput identification of human SNPs affecting regulatory element activity; citation_author=J Arensbergen; citation_volume=51; citation_issue=7; citation_publication_date=2019; citation_pages=1160-1169; citation_doi=10.1038/s41588-019-0455-2; citation_id=CR40
citation_journal_title=Br J Cancer; citation_title=Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function; citation_author=M Fagny; citation_volume=122; citation_issue=4; citation_publication_date=2020; citation_pages=569-577; citation_doi=10.1038/s41416-019-0614-3; citation_id=CR41
citation_journal_title=Oncotarget; citation_title=Single nucleotide polymorphisms and cancer susceptibility; citation_author=N Deng; citation_volume=8; citation_issue=66; citation_publication_date=2017; citation_pages=110635-110649; citation_doi=10.18632/oncotarget.22372; citation_id=CR42
citation_journal_title=Oncotarget; citation_title=SNPs in predicting clinical efficacy and toxicity of chemotherapy: walking through the quicksand; citation_author=R Palmirotta; citation_volume=9; citation_issue=38; citation_publication_date=2018; citation_pages=25355-25382; citation_doi=10.18632/oncotarget.25256; citation_id=CR43
citation_journal_title=Science; citation_title=Comprehensive mapping of long-range interactions reveals folding principles of the human genome; citation_author=E Lieberman-Aiden; citation_volume=326; citation_issue=5950; citation_publication_date=2009; citation_pages=289-293; citation_doi=10.1126/science.1181369; citation_id=CR44
citation_journal_title=Methods; citation_title=Hi-C: a comprehensive technique to capture the conformation of genomes; citation_author=JM Belton; citation_volume=58; citation_issue=3; citation_publication_date=2012; citation_pages=268-276; citation_doi=10.1016/j.ymeth.2012.05.001; citation_id=CR45
citation_journal_title=Mol Cell; citation_title=Chromatin domains: the unit of chromosome organization; citation_author=JR Dixon, DU Gorkin, B Ren; citation_volume=62; citation_issue=5; citation_publication_date=2016; citation_pages=668-680; citation_doi=10.1016/j.molcel.2016.05.018; citation_id=CR46
citation_journal_title=Nat Rev Mol Cell Biol; citation_title=Three-dimensional genome architecture: players and mechanisms; citation_author=A Pombo, N Dillon; citation_volume=16; citation_issue=4; citation_publication_date=2015; citation_pages=245-257; citation_doi=10.1038/nrm3965; citation_id=CR47
citation_journal_title=Cold Spring Harb Symp Quant Biol; citation_title=Topologically associating domains in chromosome architecture and gene regulatory landscapes during development, disease, and evolution; citation_author=R Galupa, E Heard; citation_volume=82; citation_publication_date=2017; citation_pages=267-278; citation_doi=10.1101/sqb.2017.82.035030; citation_id=CR48
citation_journal_title=Curr Opin Genet Dev; citation_title=TAD disruption as oncogenic driver; citation_author=AL Valton, J Dekker; citation_volume=36; citation_publication_date=2016; citation_pages=34-40; citation_doi=10.1016/j.gde.2016.03.008; citation_id=CR49
citation_journal_title=Cell; citation_title=A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping; citation_author=SS Rao; citation_volume=159; citation_issue=7; citation_publication_date=2014; citation_pages=1665-1680; citation_doi=10.1016/j.cell.2014.11.021; citation_id=CR50
citation_journal_title=Nature; citation_title=Human DNA methylomes at base resolution show widespread epigenomic differences; citation_author=R Lister; citation_volume=462; citation_issue=7271; citation_publication_date=2009; citation_pages=315-322; citation_doi=10.1038/nature08514; citation_id=CR51
citation_journal_title=Nat Methods; citation_title=Joint profiling of DNA methylation and chromatin architecture in single cells; citation_author=G Li; citation_volume=16; citation_issue=10; citation_publication_date=2019; citation_pages=991-993; citation_doi=10.1038/s41592-019-0502-z; citation_id=CR52
citation_journal_title=Genome Biol; citation_title=Chromatin interactome mapping at 139 independent breast cancer risk signals; citation_author=J Beesley; citation_volume=21; citation_issue=1; citation_publication_date=2020; citation_pages=8; citation_doi=10.1186/s13059-019-1877-y; citation_id=CR53
citation_journal_title=Cell Rep; citation_title=A prostate cancer risk element functions as a repressive loop that regulates HOXA13; citation_author=Z Luo; citation_volume=21; citation_issue=6; citation_publication_date=2017; citation_pages=1411-1417; citation_doi=10.1016/j.celrep.2017.10.048; citation_id=CR54
citation_journal_title=Nat Commun; citation_title=Capture Hi-C identifies the chromatin interactome of colorectal cancer risk loci; citation_author=R Jager; citation_volume=6; citation_publication_date=2015; citation_pages=6178; citation_doi=10.1038/ncomms7178; citation_id=CR55
citation_journal_title=J Cancer; citation_title=Systematic analyses of genetic variants in chromatin interaction regions identified four novel lung cancer susceptibility loci; citation_author=P Ji; citation_volume=11; citation_issue=5; citation_publication_date=2020; citation_pages=1075-1081; citation_doi=10.7150/jca.35127; citation_id=CR56
O'Mara TA, et al. Analysis of promoter-associated chromatin interactions reveals biologically relevant candidate target genes at endometrial cancer risk loci. Cancers (Basel). 2019;11(10):1440.
citation_journal_title=Nat Commun; citation_title=Capture Hi-C identifies putative target genes at 33 breast cancer risk loci; citation_author=JS Baxter; citation_volume=9; citation_issue=1; citation_publication_date=2018; citation_pages=1028; citation_doi=10.1038/s41467-018-03411-9; citation_id=CR58
citation_journal_title=Nat Commun; citation_title=Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation; citation_author=M Ghoussaini; citation_volume=4; citation_publication_date=2014; citation_pages=4999; citation_doi=10.1038/ncomms5999; citation_id=CR59
citation_journal_title=Sci Adv; citation_title=The prostate cancer risk variant rs55958994 regulates multiple gene expression through extreme long-range chromatin interaction to control tumor progression; citation_author=Y Qian; citation_volume=5; citation_issue=7; citation_publication_date=2019; citation_pages=eaaw6710; citation_doi=10.1126/sciadv.aaw6710; citation_id=CR60
citation_journal_title=Physiol Rev; citation_title=Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation; citation_author=JM Kyriakis, J Avruch; citation_volume=81; citation_issue=2; citation_publication_date=2001; citation_pages=807-869; citation_doi=10.1152/physrev.2001.81.2.807; citation_id=CR61
citation_journal_title=Biochem Cell Biol; citation_title=Wiring diagrams of MAPK regulation by MEKK1, 2, and 3; citation_author=MT Uhlik; citation_volume=82; citation_issue=6; citation_publication_date=2004; citation_pages=658-663; citation_doi=10.1139/o04-114; citation_id=CR62
citation_journal_title=Oncogene; citation_title=Role of mitogen-activated protein kinase kinase kinases in signal integration; citation_author=BD Cuevas, AN Abell, GL Johnson; citation_volume=26; citation_issue=22; citation_publication_date=2007; citation_pages=3159-3171; citation_doi=10.1038/sj.onc.1210409; citation_id=CR63
citation_journal_title=Oncotarget; citation_title=Functional significance of co-occurring mutations in PIK3CA and MAP3K1 in breast cancer; citation_author=A Avivar-Valderas; citation_volume=9; citation_issue=30; citation_publication_date=2018; citation_pages=21444-21458; citation_doi=10.18632/oncotarget.25118; citation_id=CR64
citation_journal_title=Sci Rep; citation_title=Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer; citation_author=M Michaut; citation_volume=6; citation_publication_date=2016; citation_pages=18517; citation_doi=10.1038/srep18517; citation_id=CR65
citation_journal_title=Nat Commun; citation_title=The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes; citation_author=B Pereira; citation_volume=7; citation_publication_date=2016; citation_pages=11479; citation_doi=10.1038/ncomms11479; citation_id=CR66
citation_journal_title=Am J Hum Genet; citation_title=Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1; citation_author=DM Glubb; citation_volume=96; citation_issue=1; citation_publication_date=2015; citation_pages=5-20; citation_doi=10.1016/j.ajhg.2014.11.009; citation_id=CR67
Mocellin S, et al. Breast cancer susceptibility: an integrative analysis of genomic data. bioRxiv. 2018:279984.
citation_journal_title=Cytokine Growth Factor Rev; citation_title=Cellular signaling by fibroblast growth factor receptors; citation_author=VP Eswarakumar, I Lax, J Schlessinger; citation_volume=16; citation_issue=2; citation_publication_date=2005; citation_pages=139-149; citation_doi=10.1016/j.cytogfr.2005.01.001; citation_id=CR69
citation_journal_title=Clin Cancer Res; citation_title=Targeting FGFR signaling in cancer; citation_author=M Touat; citation_volume=21; citation_issue=12; citation_publication_date=2015; citation_pages=2684-2694; citation_doi=10.1158/1078-0432.CCR-14-2329; citation_id=CR70
citation_journal_title=Nat Rev Cancer; citation_title=Fibroblast growth factor signalling: from development to cancer; citation_author=N Turner, R Grose; citation_volume=10; citation_issue=2; citation_publication_date=2010; citation_pages=116-129; citation_doi=10.1038/nrc2780; citation_id=CR71
citation_journal_title=Nat Genet; citation_title=A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer; citation_author=DJ Hunter; citation_volume=39; citation_issue=7; citation_publication_date=2007; citation_pages=870-874; citation_doi=10.1038/ng2075; citation_id=CR72
citation_journal_title=Hum Mol Genet; citation_title=FGFR2 variants and breast cancer risk: fine-scale mapping using African American studies and analysis of chromatin conformation; citation_author=MS Udler; citation_volume=18; citation_issue=9; citation_publication_date=2009; citation_pages=1692-1703; citation_doi=10.1093/hmg/ddp078; citation_id=CR73
citation_journal_title=PLoS Biol; citation_title=Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer; citation_author=KB Meyer; citation_volume=6; citation_issue=5; citation_publication_date=2008; citation_doi=10.1371/journal.pbio.0060108; citation_id=CR74
citation_journal_title=PLoS One; citation_title=FGFR2 promotes breast tumorigenicity through maintenance of breast tumor-initiating cells; citation_author=S Kim; citation_volume=8; citation_issue=1; citation_publication_date=2013; citation_doi=10.1371/journal.pone.0051671; citation_id=CR75
citation_journal_title=Carcinogenesis; citation_title=FGFR2 and other loci identified in genome-wide association studies are associated with breast cancer in African-American and younger women; citation_author=JS Barnholtz-Sloan; citation_volume=31; citation_issue=8; citation_publication_date=2010; citation_pages=1417-1423; citation_doi=10.1093/carcin/bgq128; citation_id=CR76
citation_journal_title=Am J Hum Genet; citation_title=Fine-scale mapping of the FGFR2 breast cancer risk locus: putative functional variants differentially bind FOXA1 and E2F1; citation_author=KB Meyer; citation_volume=93; citation_issue=6; citation_publication_date=2013; citation_pages=1046-1060; citation_doi=10.1016/j.ajhg.2013.10.026; citation_id=CR77
citation_journal_title=Nat Commun; citation_title=Master regulators of FGFR2 signalling and breast cancer risk; citation_author=MN Fletcher; citation_volume=4; citation_publication_date=2013; citation_pages=2464; citation_doi=10.1038/ncomms3464; citation_id=CR78
citation_journal_title=Hum Mol Genet; citation_title=The CDY-related gene family: coordinated evolution in copy number, expression profile and protein sequence; citation_author=S Dorus; citation_volume=12; citation_issue=14; citation_publication_date=2003; citation_pages=1643-1650; citation_doi=10.1093/hmg/ddg185; citation_id=CR79
citation_journal_title=J Biol Chem; citation_title=Specificity of the chromodomain Y chromosome family of chromodomains for lysine-methylated ARK(S/T) motifs; citation_author=W Fischle; citation_volume=283; citation_issue=28; citation_publication_date=2008; citation_pages=19626-19635; citation_doi=10.1074/jbc.M802655200; citation_id=CR80
citation_journal_title=J Biol Chem; citation_title=Multimerization and H3K9me3 binding are required for CDYL1b heterochromatin association; citation_author=H Franz; citation_volume=284; citation_issue=50; citation_publication_date=2009; citation_pages=35049-35059; citation_doi=10.1074/jbc.M109.052332; citation_id=CR81
citation_journal_title=Mol Cell; citation_title=CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation; citation_author=P Mulligan; citation_volume=32; citation_issue=5; citation_publication_date=2008; citation_pages=718-726; citation_doi=10.1016/j.molcel.2008.10.025; citation_id=CR82
citation_journal_title=Genes Chromosomes Cancer; citation_title=Short-form CDYLb but not long-form CDYLa functions cooperatively with histone methyltransferase G9a in hepatocellular carcinomas; citation_author=H Wu; citation_volume=52; citation_issue=7; citation_publication_date=2013; citation_pages=644-655; citation_id=CR83
citation_journal_title=iScience; citation_title=CDYL2 epigenetically regulates MIR124 to control NF-kappaB/STAT3-dependent breast cancer cell plasticity; citation_author=M Siouda; citation_volume=23; citation_issue=6; citation_publication_date=2020; citation_doi=10.1016/j.isci.2020.101141; citation_id=CR84
citation_journal_title=Theranostics; citation_title=Discrete functional and mechanistic roles of chromodomain Y-like 2 (CDYL2) transcript variants in breast cancer growth and metastasis; citation_author=LF Yang; citation_volume=10; citation_issue=12; citation_publication_date=2020; citation_pages=5242-5258; citation_doi=10.7150/thno.43744; citation_id=CR85
citation_journal_title=Am J Pathol; citation_title=Inherited genetic susceptibility to breast cancer: the beginning of the end or the end of the beginning?; citation_author=M Ghoussaini, PDP Pharoah, DF Easton; citation_volume=183; citation_issue=4; citation_publication_date=2013; citation_pages=1038-1051; citation_doi=10.1016/j.ajpath.2013.07.003; citation_id=CR86
citation_journal_title=Nat Genet; citation_title=Large-scale genotyping identifies 41 new loci associated with breast cancer risk; citation_author=K Michailidou; citation_volume=45; citation_issue=4; citation_publication_date=2013; citation_pages=353-61, 361e1-2; citation_doi=10.1038/ng.2563; citation_id=CR87
citation_journal_title=Cancer Epidemiol Biomarkers Prev; citation_title=Characterizing genetic susceptibility to breast cancer in women of African ancestry; citation_author=Y Feng; citation_volume=26; citation_issue=7; citation_publication_date=2017; citation_pages=1016-1026; citation_doi=10.1158/1055-9965.EPI-16-0567; citation_id=CR88
citation_journal_title=Cell; citation_title=The nuclear receptor superfamily: the second decade; citation_author=DJ Mangelsdorf; citation_volume=83; citation_issue=6; citation_publication_date=1995; citation_pages=835-839; citation_doi=10.1016/0092-8674(95)90199-X; citation_id=CR89
citation_journal_title=Crit Rev Eukaryot Gene Expr; citation_title=Androgen receptor: an overview; citation_author=C Chang; citation_volume=5; citation_issue=2; citation_publication_date=1995; citation_pages=97-125; citation_doi=10.1615/CritRevEukarGeneExpr.v5.i2.10; citation_id=CR90
citation_journal_title=Cancer Metastasis Rev; citation_title=Contribution of the androgen receptor to prostate cancer predisposition and progression; citation_author=G Buchanan; citation_volume=20; citation_issue=3–4; citation_publication_date=2001; citation_pages=207-223; citation_doi=10.1023/A:1015531326689; citation_id=CR91
citation_journal_title=Cancer Res; citation_title=Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease; citation_author=E LaTulippe; citation_volume=62; citation_issue=15; citation_publication_date=2002; citation_pages=4499-4506; citation_id=CR92
citation_journal_title=Nature; citation_title=The mutational landscape of lethal castration-resistant prostate cancer; citation_author=CS Grasso; citation_volume=487; citation_issue=7406; citation_publication_date=2012; citation_pages=239-243; citation_doi=10.1038/nature11125; citation_id=CR93
citation_journal_title=Mol Cell Endocrinol; citation_title=Androgen receptor (AR) aberrations in castration-resistant prostate cancer; citation_author=KK Waltering, A Urbanucci, T Visakorpi; citation_volume=360; citation_issue=1–2; citation_publication_date=2012; citation_pages=38-43; citation_doi=10.1016/j.mce.2011.12.019; citation_id=CR94
citation_journal_title=Nat Genet; citation_title=Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array; citation_author=RA Eeles; citation_volume=45; citation_issue=4; citation_publication_date=2013; citation_pages=385-91, 391e1-2; citation_doi=10.1038/ng.2560; citation_id=CR95
citation_journal_title=Nat Genet; citation_title=Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study; citation_author=Z Kote-Jarai; citation_volume=43; citation_issue=8; citation_publication_date=2011; citation_pages=785-791; citation_doi=10.1038/ng.882; citation_id=CR96
citation_journal_title=J Urol; citation_title=Association between Rs6152 polymorphism in the androgen receptor gene and disease aggressiveness in a prospective cohort of prostate cancer patients undergoing radical prostatectomy; citation_author=V Cucchiara; citation_volume=199; citation_issue=4; citation_publication_date=2018; citation_pages=E372; citation_id=CR97
citation_journal_title=Clin Genet; citation_title=A Stu I polymorphism in the human androgen receptor gene (AR); citation_author=J Lu, M Danielsen; citation_volume=49; citation_issue=6; citation_publication_date=1996; citation_pages=323-324; citation_doi=10.1111/j.1399-0004.1996.tb03800.x; citation_id=CR98
citation_journal_title=Blood; citation_title=Serum deprivation of human marrow stromal cells (hMSCs) selects for a subpopulation of early progenitor cells with enhanced expression of OCT-4 and other embryonic genes; citation_author=RR Pochampally; citation_volume=103; citation_issue=5; citation_publication_date=2004; citation_pages=1647-1652; citation_doi=10.1182/blood-2003-06-1967; citation_id=CR99
citation_journal_title=Oncol Rep; citation_title=OCT4 pseudogene 5 upregulates OCT4 expression to promote proliferation by competing with miR-145 in endometrial carcinoma; citation_author=M Bai; citation_volume=33; citation_issue=4; citation_publication_date=2015; citation_pages=1745-1752; citation_doi=10.3892/or.2015.3763; citation_id=CR100
citation_journal_title=J Biol Chem; citation_title=Multiple retropseudogenes from pluripotent cell-specific gene expression indicates a potential signature for novel gene identification; citation_author=D Pain; citation_volume=280; citation_issue=8; citation_publication_date=2005; citation_pages=6265-8; citation_doi=10.1074/jbc.C400587200; citation_id=CR101
citation_journal_title=Biochem Biophys Res Commun; citation_title=Oct4 pseudogenes are transcribed in cancers; citation_author=G Suo; citation_volume=337; citation_issue=4; citation_publication_date=2005; citation_pages=1047-1051; citation_doi=10.1016/j.bbrc.2005.09.157; citation_id=CR102
citation_journal_title=Oncogene; citation_title=The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer; citation_author=H Hayashi; citation_volume=34; citation_issue=2; citation_publication_date=2015; citation_pages=199-208; citation_doi=10.1038/onc.2013.547; citation_id=CR103
citation_journal_title=Br J Cancer; citation_title=Prospective study of DNA methylation at chromosome 8q24 in peripheral blood and prostate cancer risk; citation_author=KH Barry; citation_volume=116; citation_issue=11; citation_publication_date=2017; citation_pages=1470-1479; citation_doi=10.1038/bjc.2017.104; citation_id=CR104
citation_journal_title=Nat Genet; citation_title=Genome-wide association study of prostate cancer identifies a second risk locus at 8q24; citation_author=M Yeager; citation_volume=39; citation_issue=5; citation_publication_date=2007; citation_pages=645-649; citation_doi=10.1038/ng2022; citation_id=CR105
citation_journal_title=Am J Hum Genet; citation_title=An expressed retrogene of the master embryonic stem cell gene POU5F1 is associated with prostate cancer susceptibility; citation_author=JP Breyer; citation_volume=94; citation_issue=3; citation_publication_date=2014; citation_pages=395-404; citation_doi=10.1016/j.ajhg.2014.01.019; citation_id=CR106
citation_journal_title=J Biol Chem; citation_title=EHD2 and the novel EH domain binding protein EHBP1 couple endocytosis to the actin cytoskeleton; citation_author=A Guilherme; citation_volume=279; citation_issue=11; citation_publication_date=2004; citation_pages=10593-10605; citation_doi=10.1074/jbc.M307702200; citation_id=CR107
citation_journal_title=Onco Targets Ther; citation_title=Association between EHBP1 rs721048(A>G) polymorphism and prostate cancer susceptibility: a meta-analysis of 17 studies involving 150,678 subjects; citation_author=X Ao; citation_volume=8; citation_publication_date=2015; citation_pages=1671-1680; citation_id=CR108
citation_journal_title=J Biol Chem; citation_title=OTX1 regulates cell cycle progression of neural progenitors in the developing cerebral cortex; citation_author=B Huang; citation_volume=293; citation_issue=6; citation_publication_date=2018; citation_pages=2137-2148; citation_doi=10.1074/jbc.RA117.001249; citation_id=CR109
citation_journal_title=Cancer Sci; citation_title=Different histological types of non-small cell lung cancer have distinct folate and DNA methylation levels; citation_author=M Jin; citation_volume=100; citation_issue=12; citation_publication_date=2009; citation_pages=2325-2330; citation_doi=10.1111/j.1349-7006.2009.01321.x; citation_id=CR110
citation_journal_title=Adv Genet; citation_title=Identification of driver and passenger DNA methylation in cancer by epigenomic analysis; citation_author=S Kalari, GP Pfeifer; citation_volume=70; citation_publication_date=2010; citation_pages=277-308; citation_doi=10.1016/B978-0-12-380866-0.60010-1; citation_id=CR111
citation_journal_title=Am J Pathol; citation_title=Expression of the brain transcription factor OTX1 occurs in a subset of normal germinal-center B cells and in aggressive non-hodgkin lymphoma; citation_author=D Omodei; citation_volume=175; citation_issue=6; citation_publication_date=2009; citation_pages=2609-2617; citation_doi=10.2353/ajpath.2009.090542; citation_id=CR112
citation_journal_title=PLoS Genet; citation_title=Comprehensive functional annotation of 77 prostate cancer risk loci; citation_author=DJ Hazelett; citation_volume=10; citation_issue=1; citation_publication_date=2014; citation_doi=10.1371/journal.pgen.1004102; citation_id=CR113
citation_journal_title=Epigenetics Chromatin; citation_title=Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits; citation_author=SK Rhie; citation_volume=9; citation_publication_date=2016; citation_pages=50; citation_doi=10.1186/s13072-016-0102-4; citation_id=CR114
citation_journal_title=Genome Med; citation_title=Three-dimensional genome architecture and emerging technologies: looping in disease; citation_author=A Mishra, RD Hawkins; citation_volume=9; citation_issue=1; citation_publication_date=2017; citation_pages=87; citation_doi=10.1186/s13073-017-0477-2; citation_id=CR115
Schoenfelder S, et al. Promoter capture hi-C: high-resolution, genome-wide profiling of promoter interactions. J Vis Exp. 2018;136:57320.
citation_journal_title=Nat Commun; citation_title=Promoter-enhancer interactions identified from Hi-C data using probabilistic models and hierarchical topological domains; citation_author=G Ron; citation_volume=8; citation_issue=1; citation_publication_date=2017; citation_pages=2237; citation_doi=10.1038/s41467-017-02386-3; citation_id=CR117
citation_journal_title=Sci Rep; citation_title=Chromatin interactions and candidate genes at ten prostate cancer risk loci; citation_author=M Du; citation_volume=6; citation_publication_date=2016; citation_pages=23202; citation_doi=10.1038/srep23202; citation_id=CR118
citation_journal_title=Mol Cell; citation_title=Candidate cancer driver mutations in distal regulatory elements and long-range chromatin interaction networks; citation_author=H Zhu; citation_volume=77; citation_issue=6; citation_publication_date=2020; citation_pages=1307-1321 e10; citation_doi=10.1016/j.molcel.2019.12.027; citation_id=CR119
citation_journal_title=Genome Biol; citation_title=Functional and genetic determinants of mutation rate variability in regulatory elements of cancer genomes; citation_author=CA Lee, D Abd-Rabbo, J Reimand; citation_volume=22; citation_issue=1; citation_publication_date=2021; citation_pages=133; citation_doi=10.1186/s13059-021-02318-x; citation_id=CR120
citation_journal_title=Curr Opin Cell Biol; citation_title=The three-dimensional genome: principles and roles of long-distance interactions; citation_author=MJ Rowley, VG Corces; citation_volume=40; citation_publication_date=2016; citation_pages=8-14; citation_doi=10.1016/j.ceb.2016.01.009; citation_id=CR121
citation_journal_title=Nat Commun; citation_title=Impact of DNA methylation on 3D genome structure; citation_author=D Buitrago; citation_volume=12; citation_issue=1; citation_publication_date=2021; citation_pages=3243; citation_doi=10.1038/s41467-021-23142-8; citation_id=CR122
citation_journal_title=Cell Rep; citation_title=DNA methylation is required to maintain both DNA replication timing precision and 3D genome organization integrity; citation_author=Q Du; citation_volume=36; citation_issue=12; citation_publication_date=2021; citation_doi=10.1016/j.celrep.2021.109722; citation_id=CR123
citation_journal_title=Nature; citation_title=Insulator dysfunction and oncogene activation in IDH mutant gliomas; citation_author=WA Flavahan; citation_volume=529; citation_issue=7584; citation_publication_date=2016; citation_pages=110-114; citation_doi=10.1038/nature16490; citation_id=CR124
citation_journal_title=Nat Commun; citation_title=A high-resolution 3D epigenomic map reveals insights into the creation of the prostate cancer transcriptome; citation_author=SK Rhie; citation_volume=10; citation_issue=1; citation_publication_date=2019; citation_pages=4154; citation_doi=10.1038/s41467-019-12079-8; citation_id=CR125
citation_journal_title=Nat Protoc; citation_title=Identifying statistically significant chromatin contacts from Hi-C data with FitHiC2; citation_author=A Kaul, S Bhattacharyya, F Ay; citation_volume=15; citation_issue=3; citation_publication_date=2020; citation_pages=991-1012; citation_doi=10.1038/s41596-019-0273-0; citation_id=CR126
citation_journal_title=J Royal Stat Soc Ser B; citation_title=Controlling the false discovery rate: a practical and powerful approach to multiple testing; citation_author=Y Benjamini, Y Hochberg; citation_volume=57; citation_issue=1; citation_publication_date=1995; citation_pages=289-300; citation_id=CR127
citation_journal_title=Bioinformatics; citation_title=Identification of copy number variations and translocations in cancer cells from Hi-C data; citation_author=A Chakraborty, F Ay; citation_volume=34; citation_issue=2; citation_publication_date=2018; citation_pages=338-345; citation_doi=10.1093/bioinformatics/btx664; citation_id=CR128
citation_journal_title=Nature; citation_title=Association analysis identifies 65 new breast cancer risk loci; citation_author=K Michailidou; citation_volume=551; citation_issue=7678; citation_publication_date=2017; citation_pages=92-94; citation_doi=10.1038/nature24284; citation_id=CR129
citation_journal_title=Nat Genet; citation_title=Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci; citation_author=FR Schumacher; citation_volume=50; citation_issue=7; citation_publication_date=2018; citation_pages=928-936; citation_doi=10.1038/s41588-018-0142-8; citation_id=CR130
citation_journal_title=Genet Epidemiol; citation_title=Estimation of the multiple testing burden for genomewide association studies of nearly all common variants; citation_author=I Pe'er; citation_volume=32; citation_issue=4; citation_publication_date=2008; citation_pages=381-385; citation_doi=10.1002/gepi.20303; citation_id=CR131
citation_journal_title=Nucleic Acids Res; citation_title=HEDD: human enhancer disease database; citation_author=Z Wang; citation_volume=46; citation_issue=D1; citation_publication_date=2018; citation_pages=D113-D120; citation_doi=10.1093/nar/gkx988; citation_id=CR132
citation_journal_title=Nucleic Acids Res; citation_title=Prediction of DNA binding motifs from 3D models of transcription factors; identifying TLX3 regulated genes; citation_author=M Pujato; citation_volume=42; citation_issue=22; citation_publication_date=2014; citation_pages=13500-13512; citation_doi=10.1093/nar/gku1228; citation_id=CR133
citation_journal_title=Nat Commun; citation_title=Genome-scale identification of transcription factors that mediate an inflammatory network during breast cellular transformation; citation_author=Z Ji; citation_volume=9; citation_issue=1; citation_publication_date=2018; citation_pages=2068; citation_doi=10.1038/s41467-018-04406-2; citation_id=CR134
citation_journal_title=Genome Biol; citation_title=Identification of novel prostate cancer drivers using RegNetDriver: a framework for integration of genetic and epigenetic alterations with tissue-specific regulatory network; citation_author=P Dhingra; citation_volume=18; citation_issue=1; citation_publication_date=2017; citation_pages=141; citation_doi=10.1186/s13059-017-1266-3; citation_id=CR135
citation_journal_title=Methods; citation_title=DISEASES: text mining and data integration of disease-gene associations; citation_author=S Pletscher-Frankild; citation_volume=74; citation_publication_date=2015; citation_pages=83-89; citation_doi=10.1016/j.ymeth.2014.11.020; citation_id=CR136
citation_journal_title=Nucleic Acids Res; citation_title=TopDom: an efficient and deterministic method for identifying topological domains in genomes; citation_author=H Shin; citation_volume=44; citation_issue=7; citation_publication_date=2016; citation_doi=10.1093/nar/gkv1505; citation_id=CR137