Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.
Cancer Tomorrow [https://gco.iarc.fr/]
Haffner MC, Zwart W, Roudier MP, True LD, Nelson WG, Epstein JI, De Marzo AM, Nelson PS, Yegnasubramanian S. Genomic and phenotypic heterogeneity in prostate cancer. Nat Rev Urol. 2021;18:79–92.
Article
PubMed
Google Scholar
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71:7–33.
Article
PubMed
Google Scholar
Jamaspishvili T, Berman DM, Ross AE, Scher HI, De Marzo AM, Squire JA, Lotan TL. Clinical implications of PTEN loss in prostate cancer. Nat Rev Urol. 2018;15:222–34.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hoxhaj G, Manning BD. The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism. Nat Rev Cancer. 2020;20:74–88.
Article
CAS
PubMed
Google Scholar
Parisotto M, Grelet E, El Bizri R, Dai Y, Terzic J, Eckert D, Gargowitsch L, Bornert JM, Metzger D. PTEN deletion in luminal cells of mature prostate induces replication stress and senescence in vivo. J Exp Med. 2018;215:1749–63.
Article
CAS
PubMed
PubMed Central
Google Scholar
Koh CM, Bieberich CJ, Dang CV, Nelson WG, Yegnasubramanian S, De Marzo AM. MYC and prostate cancer. Genes Cancer. 2010;1:617–28.
Article
CAS
PubMed
PubMed Central
Google Scholar
Feinberg AP, Koldobskiy MA, Gondor A. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat Rev Genet. 2016;17:284–99.
Article
CAS
PubMed
PubMed Central
Google Scholar
Perdigoto CN. Epigenetic cancer evolution, one cell at a time. Nat Rev Genet. 2019;20:434–5.
Article
CAS
PubMed
Google Scholar
Chatterjee A, Rodger EJ, Eccles MR. Epigenetic drivers of tumourigenesis and cancer metastasis. Semin Cancer Biol. 2018;51:149–59.
Article
CAS
PubMed
Google Scholar
Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502:333–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Rao RC, Dou Y. Hijacked in cancer: the KMT2 (MLL) family of methyltransferases. Nat Rev Cancer. 2015;15:334–46.
Article
CAS
PubMed
PubMed Central
Google Scholar
Fagan RJ, Dingwall AK. COMPASS Ascending: Emerging clues regarding the roles of MLL3/KMT2C and MLL2/KMT2D proteins in cancer. Cancer Lett. 2019;458:56–65.
Article
CAS
PubMed
PubMed Central
Google Scholar
Armenia J, Wankowicz SAM, Liu D, Gao J, Kundra R, Reznik E, Chatila WK, Chakravarty D, Han GC, Coleman I, et al. The long tail of oncogenic drivers in prostate cancer. Nat Genet. 2018;50:645–51.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lavery WJ, Barski A, Wiley S, Schorry EK, Lindsley AW. KMT2C/D COMPASS complex-associated diseases [KCDCOM-ADs]: an emerging class of congenital regulopathies. Clin Epigenetics. 2020;12:10.
Article
PubMed
PubMed Central
Google Scholar
Wang L, Zhao Z, Ozark PA, Fantini D, Marshall SA, Rendleman EJ, Cozzolino KA, Louis N, He X, Morgan MA, et al. Resetting the epigenetic balance of Polycomb and COMPASS function at enhancers for cancer therapy. Nat Med. 2018;24:758–69.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lee S, Lee DK, Dou Y, Lee J, Lee B, Kwak E, Kong YY, Lee SK, Roeder RG, Lee JW. Coactivator as a target gene specificity determinant for histone H3 lysine 4 methyltransferases. Proc Natl Acad Sci U S A. 2006;103:15392–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wu X, Wu J, Huang J, Powell WC, Zhang J, Matusik RJ, Sangiorgi FO, Maxson RE, Sucov HM, Roy-Burman P. Generation of a prostate epithelial cell-specific Cre transgenic mouse model for tissue-specific gene ablation. Mech Dev. 2001;101:61–9.
Article
CAS
PubMed
Google Scholar
Cancer Genome Atlas Research Network. The Molecular taxonomy of primary prostate cancer. Cell. 2015;163:1011–25.
Article
Google Scholar
Nguyen B, Mota JM, Nandakumar S, Stopsack KH, Weg E, Rathkopf D, Morris MJ, Scher HI, Kantoff PW, Gopalan A, et al. Pan-cancer analysis of CDK12 alterations identifies a subset of prostate cancers with distinct genomic and clinical characteristics. Eur Urol. 2020;78:671–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wang S, Gao J, Lei Q, Rozengurt N, Pritchard C, Jiao J, Thomas GV, Li G, Roy-Burman P, Nelson PS, et al. Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell. 2003;4:209–21.
Article
CAS
PubMed
Google Scholar
Trotman LC, Niki M, Dotan ZA, Koutcher JA, Di Cristofano A, Xiao A, Khoo AS, Roy-Burman P, Greenberg NM, Van Dyke T, et al. Pten dose dictates cancer progression in the prostate. PLoS Biol. 2003;1:E59.
Article
PubMed
PubMed Central
Google Scholar
Suzuki A, Yamaguchi MT, Ohteki T, Sasaki T, Kaisho T, Kimura Y, Yoshida R, Wakeham A, Higuchi T, Fukumoto M, et al. T cell-specific loss of Pten leads to defects in central and peripheral tolerance. Immunity. 2001;14:523–34.
Article
CAS
PubMed
Google Scholar
Chen Z, Trotman LC, Shaffer D, Lin HK, Dotan ZA, Niki M, Koutcher JA, Scher HI, Ludwig T, Gerald W, et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature. 2005;436:725–30.
Article
CAS
PubMed
PubMed Central
Google Scholar
Aytes A, Mitrofanova A, Kinkade CW, Lefebvre C, Lei M, Phelan V, LeKaye HC, Koutcher JA, Cardiff RD, Califano A, et al. ETV4 promotes metastasis in response to activation of PI3-kinase and Ras signaling in a mouse model of advanced prostate cancer. Proc Natl Acad Sci U S A. 2013;110:E3506-3515.
Article
CAS
PubMed
PubMed Central
Google Scholar
Liberzon A, Subramanian A, Pinchback R, Thorvaldsdottir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011;27:1739–40.
Article
CAS
PubMed
PubMed Central
Google Scholar
Liberzon A, Birger C, Thorvaldsdottir H, Ghandi M, Mesirov JP, Tamayo P. The molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst. 2015;1:417–25.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gurel B, Iwata T, Koh CM, Jenkins RB, Lan F, Van Dang C, Hicks JL, Morgan J, Cornish TC, Sutcliffe S, et al. Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis. Mod Pathol. 2008;21:1156–67.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hawksworth D, Ravindranath L, Chen Y, Furusato B, Sesterhenn IA, McLeod DG, Srivastava S, Petrovics G. Overexpression of C-MYC oncogene in prostate cancer predicts biochemical recurrence. Prostate Cancer Prostatic Dis. 2010;13:311–5.
Article
CAS
PubMed
Google Scholar
Bai S, Cao S, Jin L, Kobelski M, Schouest B, Wang X, Ungerleider N, Baddoo M, Zhang W, Corey E, et al. A positive role of c-Myc in regulating androgen receptor and its splice variants in prostate cancer. Oncogene. 2019;38:4977–89.
Article
CAS
PubMed
PubMed Central
Google Scholar
Meskyte EM, Keskas S, Ciribilli Y. MYC as a multifaceted regulator of tumor microenvironment leading to metastasis. Int J Mol Sci. 2020;21(20):7710.
Article
CAS
PubMed Central
Google Scholar
Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nat Genet. 2003;33:49–54.
Article
CAS
PubMed
Google Scholar
Arias CR, Yeh HY, Soo VW. Biomarker identification for prostate cancer and lymph node metastasis from microarray data and protein interaction network using gene prioritization method. ScientificWorldJournal. 2012;2012:842727.
Article
PubMed
PubMed Central
Google Scholar
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.
Article
CAS
PubMed
Google Scholar
Collado M, Serrano M. Senescence in tumours: evidence from mice and humans. Nat Rev Cancer. 2010;10:51–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Alimonti A, Nardella C, Chen Z, Clohessy JG, Carracedo A, Trotman LC, Cheng K, Varmeh S, Kozma SC, Thomas G, et al. A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. J Clin Invest. 2010;120:681–93.
Article
CAS
PubMed
PubMed Central
Google Scholar
Sharpless NE, Sherr CJ. Forging a signature of in vivo senescence. Nat Rev Cancer. 2015;15:397–408.
Article
CAS
PubMed
Google Scholar
Guccini I, Revandkar A, D’Ambrosio M, Colucci M, Pasquini E, Mosole S, Troiani M, Brina D, Sheibani-Tezerji R, Elia AR, et al. Senescence reprogramming by TIMP1 deficiency promotes prostate cancer metastasis. Cancer Cell. 2021;39:68-82 e69.
Zhang J, Bajari R, Andric D, Gerthoffert F, Lepsa A, Nahal-Bose H, Stein LD, Ferretti V. The international cancer genome consortium data portal. Nat Biotechnol. 2019;37:367–9.
Article
CAS
PubMed
Google Scholar
Bianco-Miotto T, Chiam K, Buchanan G, Jindal S, Day TK, Thomas M, Pickering MA, O’Loughlin MA, Ryan NK, Raymond WA, et al. Global levels of specific histone modifications and an epigenetic gene signature predict prostate cancer progression and development. Cancer Epidemiol Biomarkers Prev. 2010;19:2611–22.
Dawkins JB, Wang J, Maniati E, Heward JA, Koniali L, Kocher HM, Martin SA, Chelala C, Balkwill FR, Fitzgibbon J, Grose RP. Reduced expression of histone methyltransferases KMT2C and KMT2D correlates with improved outcome in pancreatic ductal adenocarcinoma. Cancer Res. 2016;76:4861–71.
Article
CAS
PubMed
PubMed Central
Google Scholar
Sato K, Akimoto K. Expression levels of KMT2C and SLC20A1 identified by information-theoretical analysis are powerful prognostic biomarkers in estrogen receptor-positive breast cancer. Clin Breast Cancer. 2017;17:e135–42.
Article
CAS
PubMed
Google Scholar
Gala K, Li Q, Sinha A, Razavi P, Dorso M, Sanchez-Vega F, Chung YR, Hendrickson R, Hsieh JJ, Berger M, et al. KMT2C mediates the estrogen dependence of breast cancer through regulation of ERalpha enhancer function. Oncogene. 2018;37:4692–710.
Article
CAS
PubMed
PubMed Central
Google Scholar
Toska E, Osmanbeyoglu HU, Castel P, Chan C, Hendrickson RC, Elkabets M, Dickler MN, Scaltriti M, Leslie CS, Armstrong SA, Baselga J. PI3K pathway regulates ER-dependent transcription in breast cancer through the epigenetic regulator KMT2D. Science. 2017;355:1324–30.
Article
CAS
PubMed
PubMed Central
Google Scholar
Carver BS, Tran J, Gopalan A, Chen Z, Shaikh S, Carracedo A, Alimonti A, Nardella C, Varmeh S, Scardino PT, et al. Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate. Nat Genet. 2009;41:619–24.
Article
CAS
PubMed
PubMed Central
Google Scholar
Stanbrough M, Leav I, Kwan PW, Bubley GJ, Balk SP. Prostatic intraepithelial neoplasia in mice expressing an androgen receptor transgene in prostate epithelium. Proc Natl Acad Sci U S A. 2001;98:10823–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ellwood-Yen K, Graeber TG, Wongvipat J, Iruela-Arispe ML, Zhang J, Matusik R, Thomas GV, Sawyers CL. Myc-driven murine prostate cancer shares molecular features with human prostate tumors. Cancer Cell. 2003;4:223–38.
Article
CAS
PubMed
Google Scholar
Ding Z, Wu CJ, Chu GC, Xiao Y, Ho D, Zhang J, Perry SR, Labrot ES, Wu X, Lis R, et al. SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression. Nature. 2011;470:269–73.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wang J, Kobayashi T, Floc’h N, Kinkade CW, Aytes A, Dankort D, Lefebvre C, Mitrofanova A, Cardiff RD, McMahon M, et al. B-Raf activation cooperates with PTEN loss to drive c-Myc expression in advanced prostate cancer. Cancer Res. 2012;72:4765–76.
Arriaga JM, Panja S, Alshalalfa M, Zhao J, Zou M, Giacobbe A, Madubata CJ, Yeji Kim J, Rodriguez A, Coleman I, et al. A MYC and RAS co-activation signature in localized prostate cancer drives bone metastasis and castration resistance. Nat Cancer. 2020;1:1082–96.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hubbard GK, Mutton LN, Khalili M, McMullin RP, Hicks JL, Bianchi-Frias D, Horn LA, Kulac I, Moubarek MS, Nelson PS, et al. Combined MYC activation and pten loss are sufficient to create genomic instability and lethal metastatic prostate cancer. Cancer Res. 2016;76:283–92.
Article
CAS
PubMed
Google Scholar
Faget DV, Ren Q, Stewart SA. Unmasking senescence: context-dependent effects of SASP in cancer. Nat Rev Cancer. 2019;19:439–53.
Article
CAS
PubMed
Google Scholar
Chen Z, Carracedo A, Lin HK, Koutcher JA, Behrendt N, Egia A, Alimonti A, Carver BS, Gerald W, Teruya-Feldstein J, et al. Differential p53-independent outcomes of p19(Arf) loss in oncogenesis. Sci Signal. 2009;2:ra44.
Article
PubMed
PubMed Central
Google Scholar
Madden SK, de Araujo AD, Gerhardt M, Fairlie DP, Mason JM. Taking the Myc out of cancer: toward therapeutic strategies to directly inhibit c-Myc. Mol Cancer. 2021;20:3.
Article
PubMed
PubMed Central
Google Scholar
Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–4.
Article
PubMed
Google Scholar
Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:p11.
Article
Google Scholar
Bankhead P, Loughrey MB, Fernandez JA, Dombrowski Y, McArt DG, Dunne PD, McQuaid S, Gray RT, Murray LJ, Coleman HG, et al. QuPath: Open source software for digital pathology image analysis. Sci Rep. 2017;7:16878.
Article
PubMed
PubMed Central
Google Scholar
Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29:e45.
Article
CAS
PubMed
PubMed Central
Google Scholar
Drost J, Karthaus WR, Gao D, Driehuis E, Sawyers CL, Chen Y, Clevers H. Organoid culture systems for prostate epithelial and cancer tissue. Nat Protoc. 2016;11:347–58.
Article
CAS
PubMed
PubMed Central
Google Scholar
Babraham Bioinformatics [https://www.bioinformatics.babraham.ac.uk/projects/fastqc/]
Ewels P, Magnusson M, Lundin S, Kaller M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics. 2016;32:3047–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114–20.
Article
CAS
PubMed
PubMed Central
Google Scholar
Howe KL, Achuthan P, Allen J, Allen J, Alvarez-Jarreta J, Amode MR, Armean IM, Azov AG, Bennett R, Bhai J, et al. Ensembl 2021. Nucleic Acids Res. 2021;49:D884–91.
Article
CAS
PubMed
Google Scholar
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15–21.
Article
CAS
PubMed
Google Scholar
Wang L, Wang S, Li W. RSeQC: quality control of RNA-seq experiments. Bioinformatics. 2012;28:2184–5.
Article
CAS
PubMed
Google Scholar
Broad Institute. [http://broadinstitute.github.io/picard/].
Wingett SW, Andrews S. Fast Screen: A tool for multi-genome mapping and quality control. F1000Res. 2018;7:1338.
Article
PubMed
PubMed Central
Google Scholar
Liao Y, Smyth GK, Shi W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014;30:923–30.
Article
CAS
PubMed
Google Scholar
R: A language and environment for statistical computing. R Foundation for Statistical Computing [https://www.R-project.org/]
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.
Article
PubMed
PubMed Central
Google Scholar
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43:e47.
Article
PubMed
PubMed Central
Google Scholar
pheatmap: Pretty Heatmaps. R package version 1.0.12. [https://CRAN.R-project.org/package=pheatmap]
Gennady K. Fast gene set enrichment analysis. Biorxiv. 2021. https://doi.org/10.1101/060012.
Durinck S, Spellman PT, Birney E, Huber W. Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat Protoc. 2009;4:1184–91.
Article
CAS
PubMed
PubMed Central
Google Scholar
Colaprico A, Silva TC, Olsen C, Garofano L, Cava C, Garolini D, Sabedot TS, Malta TM, Pagnotta SM, Castiglioni I, et al. TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data. Nucleic Acids Res. 2016;44:e71.
Article
PubMed
Google Scholar