New insights on chromatin modifiers and histone post-translational modifications in renal cell tumours
Márcia Vieira-Coimbra
Cancer Biology & Epigenetics Group – Research Center, Portuguese Oncology Institute – Porto (IPO-Porto), Porto, Portugal
Department of Pathology, Portuguese Oncology Institute, Porto, Portugal
Search for more papers by this authorRui Henrique
Cancer Biology & Epigenetics Group – Research Center, Portuguese Oncology Institute – Porto (IPO-Porto), Porto, Portugal
Department of Pathology, Portuguese Oncology Institute, Porto, Portugal
Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
Joint senior authors.Search for more papers by this authorCorresponding Author
Carmen Jerónimo
Cancer Biology & Epigenetics Group – Research Center, Portuguese Oncology Institute – Porto (IPO-Porto), Porto, Portugal
Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
Joint senior authors.Correspondence to: Carmen Jerónimo, PhD, Cancer Biology & Epigenetics Group – Research Center (LAB3, F Bdg, 1st floor), Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino Almeida, 4200-072, Porto, Portugal. Tel.: +351 225084000; fax: + 351 225084016; e-mail: [email protected]/[email protected]Search for more papers by this authorMárcia Vieira-Coimbra
Cancer Biology & Epigenetics Group – Research Center, Portuguese Oncology Institute – Porto (IPO-Porto), Porto, Portugal
Department of Pathology, Portuguese Oncology Institute, Porto, Portugal
Search for more papers by this authorRui Henrique
Cancer Biology & Epigenetics Group – Research Center, Portuguese Oncology Institute – Porto (IPO-Porto), Porto, Portugal
Department of Pathology, Portuguese Oncology Institute, Porto, Portugal
Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
Joint senior authors.Search for more papers by this authorCorresponding Author
Carmen Jerónimo
Cancer Biology & Epigenetics Group – Research Center, Portuguese Oncology Institute – Porto (IPO-Porto), Porto, Portugal
Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
Joint senior authors.Correspondence to: Carmen Jerónimo, PhD, Cancer Biology & Epigenetics Group – Research Center (LAB3, F Bdg, 1st floor), Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino Almeida, 4200-072, Porto, Portugal. Tel.: +351 225084000; fax: + 351 225084016; e-mail: [email protected]/[email protected]Search for more papers by this authorAbstract
Renal cell tumours (RCTs) are the most common neoplasms affecting the kidney. They are clinically, pathologically and genetically heterogeneous, comprises four major histological subtypes [clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC) and chromophobe renal cell carcinoma (chRCC), which are malignant tumours, and oncocytoma, a benign tumour], as well as an increasing number of less common entities. Epigenetics has emerged as an important field in oncology due to the critical role it plays in neoplastic transformation and progression. Among epigenetic mechanisms, the modulation of chromatin packaging through covalent modifications is fundamental for gene transcription regulation and its deregulation is involved in carcinogenesis. Recently, deregulation of chromatin machinery in RCTs has increasingly acknowledged as an important mechanism for renal neoplastic transformation. The aim of this review is to summarize the most relevant alterations in histone post-translational modifications and chromatin modifiers, which have been implicated in renal tumorigenesis. The recognition of those modifications might provide new biomarkers for diagnosis and prognostication as well as novel targets for personalized therapeutic intervention.
References
- 1Ferlay JSI, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available at: http://globocan.iarc.fr. Accessed on 20 August 2014.
- 2Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014; 64: 9–29.
- 3Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med 2005; 353: 2477–90.
- 4Moch H, editor. An overview of renal cell cancer: pathology and genetics. Semin Cancer Biol 2013; 23: 3–9. Elsevier.
- 5Ljungberg B, Cowan NC, Hanbury DC, Hora M, Kuczyk MA, Merseburger AS et al. EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol 2010; 58: 398–406.
- 6Baldewijns MM, van Vlodrop IJ, Schouten LJ, Soetekouw PM, de Bruine AP, van Engeland M. Genetics and epigenetics of renal cell cancer. Biochim Biophys Acta 2008; 1785: 133–55.
- 7Jerónimo C, Henrique R. Epigenetic biomarkers in urological tumors: a systematic review. Cancer Lett 2014; 342: 264–74.
- 8Zentner GE, Henikoff S. Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol 2013; 20: 259–66.
- 9Plass C, Pfister SM, Lindroth AM, Bogatyrova O, Claus R, Lichter P. Mutations in regulators of the epigenome and their connections to global chromatin patterns in cancer. Nat Rev Genet 2013; 14: 765–80.
- 10Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res 2011; 21: 381–95.
- 11Guo G, Gui Y, Gao S, Tang A, Hu X, Huang Y et al. Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma. Nat Genet 2012; 44: 17–9.
- 12Johnson AB, Denko N, Barton MC. Hypoxia induces a novel signature of chromatin modifications and global repression of transcription. Mutat Res 2008; 640: 174–9.
- 13Chen H, Yan Y, Davidson TL, Shinkai Y, Costa M. Hypoxic stress induces dimethylated histone H3 lysine 9 through histone methyltransferase G9a in mammalian cells. Cancer Res 2006; 66: 9009–16.
- 14Mosashvilli D, Kahl P, Mertens C, Holzapfel S, Rogenhofer S, Hauser S et al. Global histone acetylation levels: prognostic relevance in patients with renal cell carcinoma. Cancer Sci 2010; 101: 2664–9.
- 15Seligson DB, Horvath S, McBrian MA, Mah V, Yu H, Tze S et al. Global levels of histone modifications predict prognosis in different cancers. Am J Pathol 2009; 174: 1619–28.
- 16Ellinger J, Kahl P, Mertens C, Rogenhofer S, Hauser S, Hartmann W et al. Prognostic relevance of global histone H3 lysine 4 (H3K4) methylation in renal cell carcinoma. Int J Cancer 2010; 127: 2360–6.
- 17Rogenhofer S, Kahl P, Mertens C, Hauser S, Hartmann W, Buttner R et al. Global histone H3 lysine 27 (H3K27) methylation levels and their prognostic relevance in renal cell carcinoma. BJU Int 2012; 109: 459–65.
- 18Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 2011; 469: 539–42.
- 19Pawłowski R, Mühl SM, Sulser T, Krek W, Moch H, Schraml P. Loss of PBRM1 expression is associated with renal cell carcinoma progression. Int J Cancer 2013; 132: E11–7.
- 20Wang X, Nagl NG Jr, Flowers S, Zweitzig D, Dallas PB, Moran E. Expression of p270 (ARID1A), a component of human SWI/SNF complexes, in human tumors. Int J Cancer 2004; 112: 636.
- 21Dalgliesh GL, Furge K, Greenman C, Chen L, Bignell G, Butler A et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 2010; 463: 360–3.
- 22Hakimi AA, Chen YB, Wren J, Gonen M, Abdel-Wahab O, Heguy A et al. Clinical and pathologic impact of select chromatin-modulating tumor suppressors in clear cell renal cell carcinoma. Eur Urol 2013; 63: 848–54.
- 23Sato Y, Yoshizato T, Shiraishi Y, Maekawa S, Okuno Y, Kamura T et al. Integrated molecular analysis of clear-cell renal cell carcinoma. Nat Genet 2013; 45: 860–7.
- 24Gossage L, Murtaza M, Slatter AF, Lichtenstein CP, Warren A, Haynes B et al. Clinical and pathological impact of VHL, PBRM1, BAP1, SETD2, KDM6A, and JARID1c in clear cell renal cell carcinoma. Genes Chromosom Cancer 2014; 53: 38–51.
- 25Duns G, van den Berg E, van Duivenbode I, Osinga J, Hollema H, Hofstra RMW et al. Histone methyltransferase gene SETD2 Is a novel tumor suppressor gene in clear cell renal cell Carcinoma. Cancer Res 2010; 70: 4287–91.
- 26van Haaften G, Dalgliesh GL, Davies H, Chen L, Bignell G, Greenman C et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet 2009; 41: 521–3.
- 27Niu X, Zhang T, Liao L, Zhou L, Lindner DJ, Zhou M et al. The von Hippel-Lindau tumor suppressor protein regulates gene expression and tumor growth through histone demethylase JARID1C. Oncogene 2012; 31: 776–86.
- 28Pena-Llopis S, Vega-Rubin-de-Celis S, Liao A, Leng N, Pavia-Jimenez A, Wang S et al. BAP1 loss defines a new class of renal cell carcinoma. Nat Genet 2012; 44: 751–9.
- 29Shen Y, Guo X, Wang Y, Qiu W, Chang Y, Zhang A et al. Expression and significance of histone H3K27 demethylases in renal cell carcinoma. BMC Cancer 2012; 12: 470.
- 30Sakurai T, Bilim VN, Ugolkov AV, Yuuki K, Tsukigi M, Motoyama T et al. The enhancer of zeste homolog 2 (EZH2), a potential therapeutic target, is regulated by miR-101 in renal cancer cells. Biochem Biophys Res Commun 2012; 422: 607–14.
- 31Fritzsche FR, Weichert W, Roske A, Gekeler V, Beckers T, Stephan C, et al. Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer. BMC Cancer 2008; 8: 381.
- 32Cha TL, Chuang MJ, Wu ST, Sun GH, Chang SY, Yu DS, et al. Dual degradation of aurora A and B kinases by the histone deacetylase inhibitor LBH589 induces G2-M arrest and apoptosis of renal cancer cells. Clin Cancer Res 2009; 15: 840–50.
- 33Beyer S, Kristensen MM, Jensen KS, Johansen JV, Staller P. The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF. J Biol Chem 2008; 283: 36542–52.
- 34Krieg AJ, Rankin EB, Chan D, Razorenova O, Fernandez S, Giaccia AJ. Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth. Mol Cell Biol 2010; 30: 344–53.
- 35Qian DZ, Kachhap SK, Collis SJ, Verheul HM, Carducci MA, Atadja P et al. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Res 2006; 66: 8814–21.
- 36Wagener N, Macher-Goeppinger S, Pritsch M, Husing J, Hoppe-Seyler K, Schirmacher P et al. Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma. BMC Cancer 2010; 10: 524.
- 37Khan O, La Thangue NB. HDAC inhibitors in cancer biology: emerging mechanisms and clinical applications. Immunol Cell Biol 2012; 90: 85–94.
- 38Jones J, Juengel E, Mickuckyte A, Hudak L, Wedel S, Jonas D et al. The histone deacetylase inhibitor valproic acid alters growth properties of renal cell carcinoma in vitro and in vivo. J Cell Mol Med 2009; 13: 2376–85.
- 39Siu LL, Pili R, Duran I, Messersmith WA, Chen EX, Sullivan R et al. Phase I study of MGCD0103 given as a three-times-per-week oral dose in patients with advanced solid tumors. J Clin Oncol 2008; 26: 1940–7.
- 40Stadler WM, Margolin K, Ferber S, McCulloch W, Thompson JA. A phase II study of depsipeptide in refractory metastatic renal cell cancer. Clin Genitourin Cancer 2006; 5: 57–60.
- 41Hainsworth JD, Infante JR, Spigel DR, Arrowsmith ER, Boccia RV, Burris HA. A phase II trial of panobinostat, a histone deacetylase inhibitor, in the treatment of patients with refractory metastatic renal cell carcinoma. Cancer Invest 2011; 29: 451–5.
- 42Touma SE, Goldberg JS, Moench P, Guo X, Tickoo SK, Gudas LJ et al. Retinoic acid and the histone deacetylase inhibitor trichostatin a inhibit the proliferation of human renal cell carcinoma in a xenograft tumor model. Clin Cancer Res 2005; 11: 3558–66.
- 43Wang XF, Qian DZ, Ren M, Kato Y, Wei Y, Zhang L et al. Epigenetic modulation of retinoic acid receptor beta2 by the histone deacetylase inhibitor MS-275 in human renal cell carcinoma. Clin Cancer Res 2005; 11: 3535–42.
- 44Mahalingam D, Medina EC, Esquivel JA 2nd, Espitia CM, Smith S, Oberheu K et al. Vorinostat enhances the activity of temsirolimus in renal cell carcinoma through suppression of survivin levels. Clin Cancer Res 2010; 16: 141–53.
- 45Spannhoff A, Sippl W, Jung M. Cancer treatment of the future: inhibitors of histone methyltransferases. Int J Biochem Cell Biol 2009; 41: 4–11.
- 46Liu L, Xu Z, Zhong L, Wang H, Jiang S, Long Q et al. EZH2 promotes tumor cell migration and invasion via epigenetic repression of E-cadherin in renal cell carcinoma. BJU Int 2014;doi:10.1111/bju12702.
- 47Henrique R, Luis AS, Jeronimo C. The epigenetics of renal cell tumors: from biology to biomarkers. Front Genet 2012; 3: 94.
- 48Neal CS, Michael MZ, Rawlings LH, Van der Hoek MB, Gleadle JM. The VHL-dependent regulation of microRNAs in renal cancer. BMC Med 2010; 8: 64.
- 49Silva-Santos RM, Costa-Pinheiro P, Luis A, Antunes L, Lobo F, Oliveira J et al. MicroRNA profile: a promising ancillary tool for accurate renal cell tumour diagnosis. Br J Cancer 2013; 109: 2646–53.
- 50Cha ST, Chen PS, Johansson G, Chu CY, Wang MY, Jeng YM et al. MicroRNA-519c suppresses hypoxia-inducible factor-1alpha expression and tumor angiogenesis. Cancer Res 2010; 70: 2675–85.
