Targeting Melanoma: Unusual Epigenetics Reveals the Dynamic Rewiring of Metastatic Cells

EpigenomicsVol. 7, No. 7 EditorialTargeting melanoma: unusual epigenetics reveals the dynamic rewiring of metastatic cellsMiguel Vizoso & Manel EstellerMiguel Vizoso Epigenetics & Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain & Manel Esteller*Author for correspondence: E-mail Address: mesteller@idibell.cat Epigenetics & Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain Department of Physiological Sciences II, School of Medicine, University of Barcelona, 08007 Barcelona, Catalonia, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Catalonia, SpainPublished Online:6 Nov 2015https://doi.org/10.2217/epi.15.67AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: cryptic promoterDNA hypomethylationdrug sensitivitymelanoma biomarkerTBC1D16References1 Goll MG, Bestor TH. Eukaryotic cytosine methyltransferases. Annu. Rev. Biochem. 74, 481–514 (2005).Crossref, Medline, CAS, Google Scholar2 Robertson KD. DNA methylation, methyltransferases, and cancer. Oncogene 20, 3139–3155 (2001).Crossref, Medline, CAS, Google Scholar3 Fernandez AF, Assenov Y, Martin-Subero JI et al. A DNA methylation fingerprint of 1628 human samples. Genome Res. 22, 407–19 (2012).Crossref, Medline, CAS, Google Scholar4 Esteller M, Garcia-Foncillas J, Andion E et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N. Engl. J. Med. 343, 1350–1354 (2000).Crossref, Medline, CAS, Google Scholar5 Esteller M, Silva JM, Dominguez G et al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J. Natl Cancer Inst. 92, 564–569 (2000).Crossref, Medline, CAS, Google Scholar6 Esteller M. Epigenetics in cancer. N. Engl. J. Med. 358, 1148–59 (2008).Crossref, Medline, CAS, Google Scholar7 Esteller M. Aberrant DNA methylation as a cancer-inducing mechanism. Annu. Rev. Pharmacol. Toxicol. 45, 629–656 (2005).Crossref, Medline, CAS, Google Scholar8 Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N. Engl. J. Med. 349, 2042–2054 (2003).Crossref, Medline, CAS, Google Scholar9 Moutinho C, Martinez-Cardus A, Santos C et al. Epigenetic inactivation of the BRCA1 interactor SRBC and resistance to oxaliplatin in colorectal cancer. J. Natl Cancer Inst. 106, djt322 (2014).Crossref, Medline, Google Scholar10 Sandoval J, Mendez-Gonzalez J, Nadal E et al. A prognostic DNA methylation signature for stage I non-small-cell lung cancer. J. Clin. Oncol. 31, 4140–4147 (2013).Crossref, Medline, Google Scholar11 Rhee I, Jair KW, Yen RW et al. CpG methylation is maintained in human cancer cells lacking DNMT1. Nature 404, 1003–1007 (2000).Crossref, Medline, CAS, Google Scholar12 Rhee I, Bachman KE, Park BH et al. DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 416, 552–556 (2002).Crossref, Medline, CAS, Google Scholar13 Jin B, Robertson KD. DNA methyltransferases, DNA damage repair, and cancer. Adv. Exp. Med. Biol. 754, 3–29 (2013).Crossref, Medline, CAS, Google Scholar14 Tahiliani M, Koh KP, Shen Y et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930–935 (2009).Crossref, Medline, CAS, Google Scholar15 Williams K, Christensen J, Helin K. DNA methylation: TET proteins-guardians of CpG islands? EMBO Rep. 13, 28–35 (2012).Crossref, CAS, Google Scholar16 Vizoso M, Ferreira HJ, Lopez-Serra P et al. Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR. Nat. Med. 21(7), 741–750 (2015).Crossref, Medline, CAS, Google Scholar17 Akavia UD, Litvin O, Kim J et al. An integrated approach to uncover drivers of cancer. Cell 143, 1005–1017 (2010).Crossref, Medline, CAS, Google Scholar18 Goueli BS, Powell MB, Finger EC et al. TBC1D16 is a Rab4A GTPase activating protein that regulates receptor recycling and EGF receptor signaling. Proc. Natl Acad. Sci. USA 109, 15787–15792 (2012).Crossref, Medline, CAS, Google Scholar19 Wagle N, Emery C, Berger MF et al. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J. Clin. Oncol. 29, 3085–3096 (2011).Crossref, Medline, CAS, Google Scholar20 Robert C, Karaszewska B, Schachter J et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N. Engl. J. Med. 372, 30–39 (2015).Crossref, Medline, CAS, Google Scholar21 Larkin J, Chiarion-Sileni V, Gonzalez R et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373(1), 23–34 (2015).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByTre2-Bub2-Cdc16 Family Proteins Based Nomogram Serve as a Promising Prognosis Predicting Model for Melanoma28 October 2020 | Frontiers in Oncology, Vol. 10Epigenetics of skin cancer: Interventions by selected bioactive phytochemicals3 November 2017 | Photodermatology, Photoimmunology & Photomedicine, Vol. 34, No. 1 Vol. 7, No. 7 Follow us on social media for the latest updates Metrics Downloaded 78 times History Published online 6 November 2015 Published in print October 2015 Information© Future Medicine LtdKeywordscryptic promoterDNA hypomethylationdrug sensitivitymelanoma biomarker TBC1D16 AcknowledgementsThe authors thank the patients and their families.Financial & competing interests disclosureThe research leading to these results has received funding from the European Community's Seventh Framework Programme FP7/2007–2013 under grant agreement no. PIAPP-GA-2009-230614-Target-Melanoma project (M Esteller), the Worldwide Cancer Research grant reference no. 15-0354 (M Esteller), the European Research Council Advanced grant no. 268626-EPINORC project (M Esteller), the Ministerio de Ciencia e Innovación grant numbers SAF2011-22803 (M Esteller), the Cellex Foundation (M Esteller) and 2014-SGR 633 (M Esteller). M Vizoso was supported by a Formación de Profesorado Universitario fellowship from the Spanish Ministry of Education. M Esteller is an Institucio Catalana de Recerca i Estudis Avançats Research Professor. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download