Skip to main content
Top
Published in: Journal of Hematology & Oncology 1/2015

Open Access 01-12-2015 | Review

Role of DNA methylation in renal cell carcinoma

Authors: Niraj Shenoy, Nishanth Vallumsetla, Yiyu Zou, Jose Nahun Galeas, Makardhwaj Shrivastava, Caroline Hu, Katalin Susztak, Amit Verma

Published in: Journal of Hematology & Oncology | Issue 1/2015

Login to get access

Abstract

Alterations in DNA methylation are seen in cancers and have also been examined in clear cell renal cell carcinoma (ccRCC). Numerous tumor suppressor genes have been reported to be partially or completely silenced due to hypermethylation of their promoters in single-locus studies, and the use of hypomethylating agents has been shown to restore the expression of many of these genes in vitro. In particular, members of the Wnt and TGF-beta pathways, pro-apoptotic genes such as APAF-1 and negative cell-cycle regulators such as KILLIN have been shown to be epigenetically silenced in numerous studies in ccRCC. Recently, TCGA analysis of a large cohort of ccRCC samples demonstrated that aberrant hypermethylation correlated with the stage and grade in kidney cancer. Our genome-wide studies also revealed aberrant widespread hypermethylation that affected regulatory regions of the kidney genome in ccRCC. We also observed that aberrant enhancer hypermethylation was predictive of adverse prognosis in ccRCC. Recent discovery of mutations affecting epigenetic regulators reinforces the importance of these changes in the pathophysiology of ccRCC and points to the potential of epigenetic modulators in the treatment of this malignancy.
Literature
1.
go back to reference Katoh M, Katoh M. WNT signaling pathway and stem cell signaling network. Clin Cancer Res. 2007;13(14):4042–5.PubMedCrossRef Katoh M, Katoh M. WNT signaling pathway and stem cell signaling network. Clin Cancer Res. 2007;13(14):4042–5.PubMedCrossRef
2.
3.
go back to reference Gumz ML et al. Secreted frizzled-related protein 1 loss contributes to tumor phenotype of clear cell renal cell carcinoma. Clin Cancer Res. 2007;13(16):4740–9.PubMedCrossRef Gumz ML et al. Secreted frizzled-related protein 1 loss contributes to tumor phenotype of clear cell renal cell carcinoma. Clin Cancer Res. 2007;13(16):4740–9.PubMedCrossRef
4.
go back to reference Gloerich M, Bos JL. Regulating Rap small G-proteins in time and space. Trends Cell Biol. 2011;21(10):615–23.PubMedCrossRef Gloerich M, Bos JL. Regulating Rap small G-proteins in time and space. Trends Cell Biol. 2011;21(10):615–23.PubMedCrossRef
5.
go back to reference Gloerich M, Bos JL. Epac: defining a new mechanism for cAMP action. Annu Rev Pharmacol Toxicol. 2010;50:355–75.PubMedCrossRef Gloerich M, Bos JL. Epac: defining a new mechanism for cAMP action. Annu Rev Pharmacol Toxicol. 2010;50:355–75.PubMedCrossRef
8.
go back to reference Bennett KL et al. Germline and somatic DNA methylation and epigenetic regulation of KILLIN in renal cell carcinoma. Genes Chromosomes Cancer. 2011;50(8):654–61.PubMedCentralPubMedCrossRef Bennett KL et al. Germline and somatic DNA methylation and epigenetic regulation of KILLIN in renal cell carcinoma. Genes Chromosomes Cancer. 2011;50(8):654–61.PubMedCentralPubMedCrossRef
9.
go back to reference Polakis P. Wnt signaling and cancer. Genes Dev. 2000;14(15):1837–51.PubMed Polakis P. Wnt signaling and cancer. Genes Dev. 2000;14(15):1837–51.PubMed
10.
go back to reference Kawakami K et al. Functional significance of Wnt inhibitory factor-1 gene in kidney cancer. Cancer Res. 2009;69(22):8603–10.PubMedCrossRef Kawakami K et al. Functional significance of Wnt inhibitory factor-1 gene in kidney cancer. Cancer Res. 2009;69(22):8603–10.PubMedCrossRef
11.
go back to reference Hirata H et al. Wnt antagonist DKK1 acts as a tumor suppressor gene that induces apoptosis and inhibits proliferation in human renal cell carcinoma. Int J Cancer. 2011;128(8):1793–803.PubMedCrossRef Hirata H et al. Wnt antagonist DKK1 acts as a tumor suppressor gene that induces apoptosis and inhibits proliferation in human renal cell carcinoma. Int J Cancer. 2011;128(8):1793–803.PubMedCrossRef
12.
go back to reference Kawamoto K et al. DNA methylation and histone modifications cause silencing of Wnt antagonist gene in human renal cell carcinoma cell lines. Int J Cancer. 2008;123(3):535–42.PubMedCrossRef Kawamoto K et al. DNA methylation and histone modifications cause silencing of Wnt antagonist gene in human renal cell carcinoma cell lines. Int J Cancer. 2008;123(3):535–42.PubMedCrossRef
13.
go back to reference Awakura Y et al. Methylation-associated silencing of SFRP1 in renal cell carcinoma. Oncol Rep. 2008;20(5):1257–63.PubMed Awakura Y et al. Methylation-associated silencing of SFRP1 in renal cell carcinoma. Oncol Rep. 2008;20(5):1257–63.PubMed
14.
go back to reference Dahl E et al. Frequent loss of SFRP1 expression in multiple human solid tumours: association with aberrant promoter methylation in renal cell carcinoma. Oncogene. 2007;26(38):5680–91.PubMedCrossRef Dahl E et al. Frequent loss of SFRP1 expression in multiple human solid tumours: association with aberrant promoter methylation in renal cell carcinoma. Oncogene. 2007;26(38):5680–91.PubMedCrossRef
15.
go back to reference Kawakami K et al. Secreted frizzled-related protein-5 is epigenetically downregulated and functions as a tumor suppressor in kidney cancer. Int J Cancer. 2011;128(3):541–50.PubMedCentralPubMedCrossRef Kawakami K et al. Secreted frizzled-related protein-5 is epigenetically downregulated and functions as a tumor suppressor in kidney cancer. Int J Cancer. 2011;128(3):541–50.PubMedCentralPubMedCrossRef
19.
go back to reference Hildebrandt MAT et al. Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. Oncogene. 2010;29(42):5724–8.PubMedCrossRef Hildebrandt MAT et al. Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. Oncogene. 2010;29(42):5724–8.PubMedCrossRef
20.
go back to reference Brazil DP et al. BMP signalling: agony and antagony in the family. Trends Cell Biol. 2015;25(5):249–64.PubMedCrossRef Brazil DP et al. BMP signalling: agony and antagony in the family. Trends Cell Biol. 2015;25(5):249–64.PubMedCrossRef
21.
go back to reference van Vlodrop IJ et al. Prognostic significance of Gremlin1 (GREM1) promoter CpG island hypermethylation in clear cell renal cell carcinoma. Am J Pathol. 2010;176(2):575–84.PubMedCentralPubMedCrossRef van Vlodrop IJ et al. Prognostic significance of Gremlin1 (GREM1) promoter CpG island hypermethylation in clear cell renal cell carcinoma. Am J Pathol. 2010;176(2):575–84.PubMedCentralPubMedCrossRef
23.
go back to reference Majid S et al. BTG3 tumor suppressor gene promoter demethylation, histone modification and cell cycle arrest by genistein in renal cancer. Carcinogenesis. 2009;30(4):662–70.PubMedCentralPubMedCrossRef Majid S et al. BTG3 tumor suppressor gene promoter demethylation, histone modification and cell cycle arrest by genistein in renal cancer. Carcinogenesis. 2009;30(4):662–70.PubMedCentralPubMedCrossRef
24.
go back to reference Leaman DW et al. Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis. J Biol Chem. 2002;277(32):28504–11.PubMedCrossRef Leaman DW et al. Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis. J Biol Chem. 2002;277(32):28504–11.PubMedCrossRef
25.
go back to reference Reu FJ et al. Overcoming resistance to interferon-induced apoptosis of renal carcinoma and melanoma cells by DNA demethylation. J Clin Oncol. 2006;24(23):3771–9.PubMedCrossRef Reu FJ et al. Overcoming resistance to interferon-induced apoptosis of renal carcinoma and melanoma cells by DNA demethylation. J Clin Oncol. 2006;24(23):3771–9.PubMedCrossRef
26.
go back to reference Ahmad ST et al. Methylation of the APAF-1 and DAPK-1 promoter region correlates with progression of renal cell carcinoma in North Indian population. Tumor Biol. 2012;33(2):395–402.CrossRef Ahmad ST et al. Methylation of the APAF-1 and DAPK-1 promoter region correlates with progression of renal cell carcinoma in North Indian population. Tumor Biol. 2012;33(2):395–402.CrossRef
27.
go back to reference Christoph F et al. Methylation of tumour suppressor genes APAF-1 and DAPK-1 and in vitro effects of demethylating agents in bladder and kidney cancer. Br J Cancer. 2006;95(12):1701–7.PubMedCentralPubMedCrossRef Christoph F et al. Methylation of tumour suppressor genes APAF-1 and DAPK-1 and in vitro effects of demethylating agents in bladder and kidney cancer. Br J Cancer. 2006;95(12):1701–7.PubMedCentralPubMedCrossRef
28.
go back to reference Raveh T et al. DAP kinase activates a p19ARF/p53-mediated apoptotic checkpoint to suppress oncogenic transformation. Nat Cell Biol. 2001;3(1):1–7.PubMedCrossRef Raveh T et al. DAP kinase activates a p19ARF/p53-mediated apoptotic checkpoint to suppress oncogenic transformation. Nat Cell Biol. 2001;3(1):1–7.PubMedCrossRef
29.
go back to reference Gillissen B et al. Induction of cell death by the BH3-only Bcl-2 homolog Nbk/Bik is mediated by an entirely Bax-dependent mitochondrial pathway. EMBO J. 2003;22(14):3580–90.PubMedCentralPubMedCrossRef Gillissen B et al. Induction of cell death by the BH3-only Bcl-2 homolog Nbk/Bik is mediated by an entirely Bax-dependent mitochondrial pathway. EMBO J. 2003;22(14):3580–90.PubMedCentralPubMedCrossRef
30.
go back to reference Okuda H et al. Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma. Oncogene. 2006;25(12):1733–42.PubMedCrossRef Okuda H et al. Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma. Oncogene. 2006;25(12):1733–42.PubMedCrossRef
31.
go back to reference Tran YK et al. A novel member of the NF2/ERM/4.1 superfamily with growth suppressing properties in lung cancer. Cancer Res. 1999;59(1):35–43.PubMed Tran YK et al. A novel member of the NF2/ERM/4.1 superfamily with growth suppressing properties in lung cancer. Cancer Res. 1999;59(1):35–43.PubMed
32.
go back to reference Yamada D et al. Promoter hypermethylation of the potential tumor suppressor DAL-1/4.1B gene in renal clear cell carcinoma. Int J Cancer. 2006;118(4):916–23.PubMedCrossRef Yamada D et al. Promoter hypermethylation of the potential tumor suppressor DAL-1/4.1B gene in renal clear cell carcinoma. Int J Cancer. 2006;118(4):916–23.PubMedCrossRef
34.
go back to reference Morris MR et al. Tumor suppressor activity and epigenetic inactivation of hepatocyte growth factor activator inhibitor type 2/SPINT2 in papillary and clear cell renal cell carcinoma. Cancer Res. 2005;65(11):4598–606.PubMedCrossRef Morris MR et al. Tumor suppressor activity and epigenetic inactivation of hepatocyte growth factor activator inhibitor type 2/SPINT2 in papillary and clear cell renal cell carcinoma. Cancer Res. 2005;65(11):4598–606.PubMedCrossRef
35.
go back to reference Syrigos KN et al. Altered gamma-catenin expression correlates with poor survival in patients with bladder cancer. J Urol. 1998;160(5):1889–93.PubMedCrossRef Syrigos KN et al. Altered gamma-catenin expression correlates with poor survival in patients with bladder cancer. J Urol. 1998;160(5):1889–93.PubMedCrossRef
36.
go back to reference Cerrato A et al. Beta- and gamma-catenin expression in thyroid carcinomas. J Pathol. 1998;185(3):267–72.PubMedCrossRef Cerrato A et al. Beta- and gamma-catenin expression in thyroid carcinomas. J Pathol. 1998;185(3):267–72.PubMedCrossRef
37.
go back to reference Pantel K et al. Reduced expression of plakoglobin indicates an unfavorable prognosis in subsets of patients with non-small-cell lung cancer. J Clin Oncol. 1998;16(4):1407–13.PubMed Pantel K et al. Reduced expression of plakoglobin indicates an unfavorable prognosis in subsets of patients with non-small-cell lung cancer. J Clin Oncol. 1998;16(4):1407–13.PubMed
38.
go back to reference Smith LT et al. Epigenetic regulation of the tumor suppressor gene TCF21 on 6q23-q24 in lung and head and neck cancer. Proc Natl Acad Sci USA. 2006;103(4):982–7.PubMedCentralPubMedCrossRef Smith LT et al. Epigenetic regulation of the tumor suppressor gene TCF21 on 6q23-q24 in lung and head and neck cancer. Proc Natl Acad Sci USA. 2006;103(4):982–7.PubMedCentralPubMedCrossRef
39.
go back to reference Ye YW et al. Down-regulation of TCF21 is associated with poor survival in clear cell renal cell carcinoma. Neoplasma. 2012;59(6):599–605.PubMedCrossRef Ye YW et al. Down-regulation of TCF21 is associated with poor survival in clear cell renal cell carcinoma. Neoplasma. 2012;59(6):599–605.PubMedCrossRef
40.
go back to reference Costa VL et al. TCF21 and PCDH17 methylation: an innovative panel of biomarkers for a simultaneous detection of urological cancers. Epigenetics. 2011;6(9):1120–30.PubMedCrossRef Costa VL et al. TCF21 and PCDH17 methylation: an innovative panel of biomarkers for a simultaneous detection of urological cancers. Epigenetics. 2011;6(9):1120–30.PubMedCrossRef
41.
go back to reference Chen WY et al. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell. 2005;123(3):437–48.PubMedCrossRef Chen WY et al. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell. 2005;123(3):437–48.PubMedCrossRef
42.
go back to reference Wang CG et al. Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol. 2006;8(9):1025–U109.PubMedCrossRef Wang CG et al. Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol. 2006;8(9):1025–U109.PubMedCrossRef
43.
go back to reference Jenal M et al. The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1. Mol Cancer Res. 2009;7(6):916–22.PubMedCrossRef Jenal M et al. The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1. Mol Cancer Res. 2009;7(6):916–22.PubMedCrossRef
44.
go back to reference Eggers H et al. Prognostic and diagnostic relevance of hypermethylated in cancer 1 (HIC1) CpG island methylation in renal cell carcinoma. Int J Oncol. 2012;40(5):1650–8.PubMed Eggers H et al. Prognostic and diagnostic relevance of hypermethylated in cancer 1 (HIC1) CpG island methylation in renal cell carcinoma. Int J Oncol. 2012;40(5):1650–8.PubMed
45.
go back to reference Kim M et al. LRRC3B, encoding a leucine-rich repeat-containing protein, is a putative tumor suppressor gene in gastric cancer. Cancer Res. 2008;68(17):7147–55.PubMedCrossRef Kim M et al. LRRC3B, encoding a leucine-rich repeat-containing protein, is a putative tumor suppressor gene in gastric cancer. Cancer Res. 2008;68(17):7147–55.PubMedCrossRef
46.
go back to reference Haraldson K et al. LRRC3B gene is frequently epigenetically inactivated in several epithelial malignancies and inhibits cell growth and replication. Biochimie. 2012;94(5):1151–7.PubMedCrossRef Haraldson K et al. LRRC3B gene is frequently epigenetically inactivated in several epithelial malignancies and inhibits cell growth and replication. Biochimie. 2012;94(5):1151–7.PubMedCrossRef
47.
go back to reference Merika M, Orkin SH. DNA-binding specificity of GATA family transcription factors. Mol Cell Biol. 1993;13(7):3999–4010.PubMedCentralPubMed Merika M, Orkin SH. DNA-binding specificity of GATA family transcription factors. Mol Cell Biol. 1993;13(7):3999–4010.PubMedCentralPubMed
48.
go back to reference Peters I et al. GATA5 CpG island methylation in renal cell cancer: a potential biomarker for metastasis and disease progression. BJU Int. 2012;110(2 Pt 2):E144–52.PubMedCrossRef Peters I et al. GATA5 CpG island methylation in renal cell cancer: a potential biomarker for metastasis and disease progression. BJU Int. 2012;110(2 Pt 2):E144–52.PubMedCrossRef
49.
go back to reference Morrissey C et al. Epigenetic inactivation of the RASSF1A 3p21.3 tumor suppressor gene in both clear cell and papillary renal cell carcinoma. Cancer Res. 2001;61(19):7277–81.PubMed Morrissey C et al. Epigenetic inactivation of the RASSF1A 3p21.3 tumor suppressor gene in both clear cell and papillary renal cell carcinoma. Cancer Res. 2001;61(19):7277–81.PubMed
50.
go back to reference Peters I et al. RASSF1A promoter methylation and expression analysis in normal and neoplastic kidney indicates a role in early tumorigenesis. Mol Cancer. 2007;6:49.PubMedCentralPubMedCrossRef Peters I et al. RASSF1A promoter methylation and expression analysis in normal and neoplastic kidney indicates a role in early tumorigenesis. Mol Cancer. 2007;6:49.PubMedCentralPubMedCrossRef
51.
go back to reference Ellinger J et al. DNA hypermethylation in papillary renal cell carcinoma. BJU Int. 2011;107(4):664–9.PubMedCrossRef Ellinger J et al. DNA hypermethylation in papillary renal cell carcinoma. BJU Int. 2011;107(4):664–9.PubMedCrossRef
52.
go back to reference Kawai Y et al. Methylation level of the RASSF1A promoter is an independent prognostic factor for clear-cell renal cell carcinoma. Ann Oncol. 2010;21(8):1612–7.PubMedCrossRef Kawai Y et al. Methylation level of the RASSF1A promoter is an independent prognostic factor for clear-cell renal cell carcinoma. Ann Oncol. 2010;21(8):1612–7.PubMedCrossRef
54.
55.
56.
go back to reference Lv D et al. Genetic and epigenetic control of UNC5C expression in human renal cell carcinoma. Eur J Cancer. 2011;47(13):2068–76.PubMedCrossRef Lv D et al. Genetic and epigenetic control of UNC5C expression in human renal cell carcinoma. Eur J Cancer. 2011;47(13):2068–76.PubMedCrossRef
57.
go back to reference Bader BL, Jahn L, Franke WW. Low level expression of cytokeratins 8, 18 and 19 in vascular smooth muscle cells of human umbilical cord and in cultured cells derived therefrom, with an analysis of the chromosomal locus containing the cytokeratin 19 gene. Eur J Cell Biol. 1988;47(2):300–19.PubMed Bader BL, Jahn L, Franke WW. Low level expression of cytokeratins 8, 18 and 19 in vascular smooth muscle cells of human umbilical cord and in cultured cells derived therefrom, with an analysis of the chromosomal locus containing the cytokeratin 19 gene. Eur J Cell Biol. 1988;47(2):300–19.PubMed
58.
go back to reference Ju JH et al. Regulation of cell proliferation and migration by keratin19-induced nuclear import of early growth response-1 in breast cancer cells. Clin Cancer Res. 2013;19(16):4335–46.PubMedCrossRef Ju JH et al. Regulation of cell proliferation and migration by keratin19-induced nuclear import of early growth response-1 in breast cancer cells. Clin Cancer Res. 2013;19(16):4335–46.PubMedCrossRef
59.
go back to reference Cao Y et al. Expression of MUC1, Thomsen-Friedenreich-related antigens, and cytokeratin 19 in human renal cell carcinomas and tubular clear cell lesions. Virchows Arch. 2000;436(2):119–26.PubMedCrossRef Cao Y et al. Expression of MUC1, Thomsen-Friedenreich-related antigens, and cytokeratin 19 in human renal cell carcinomas and tubular clear cell lesions. Virchows Arch. 2000;436(2):119–26.PubMedCrossRef
60.
go back to reference Labastie MC et al. The Gata-3 gene is expressed during human kidney embryogenesis. Kidney Int. 1995;47(6):1597–603.PubMedCrossRef Labastie MC et al. The Gata-3 gene is expressed during human kidney embryogenesis. Kidney Int. 1995;47(6):1597–603.PubMedCrossRef
61.
go back to reference Cooper SJ et al. Loss of type III transforming growth factor-beta receptor expression is due to methylation silencing of the transcription factor GATA3 in renal cell carcinoma. Oncogene. 2010;29(20):2905–15.PubMedCentralPubMedCrossRef Cooper SJ et al. Loss of type III transforming growth factor-beta receptor expression is due to methylation silencing of the transcription factor GATA3 in renal cell carcinoma. Oncogene. 2010;29(20):2905–15.PubMedCentralPubMedCrossRef
62.
go back to reference Tavares TS et al. Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008;7(10):1607–18.PubMedCentralPubMedCrossRef Tavares TS et al. Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008;7(10):1607–18.PubMedCentralPubMedCrossRef
63.
go back to reference Qi JH et al. A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med. 2003;9(4):407–15.PubMedCrossRef Qi JH et al. A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med. 2003;9(4):407–15.PubMedCrossRef
64.
go back to reference Masson D et al. Loss of expression of TIMP3 in clear cell renal cell carcinoma. Eur J Cancer. 2010;46(8):1430–7.PubMedCrossRef Masson D et al. Loss of expression of TIMP3 in clear cell renal cell carcinoma. Eur J Cancer. 2010;46(8):1430–7.PubMedCrossRef
65.
go back to reference Bachman KE et al. Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggest a suppressor role in kidney, brain, and other human cancers. Cancer Res. 1999;59(4):798–802.PubMed Bachman KE et al. Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggest a suppressor role in kidney, brain, and other human cancers. Cancer Res. 1999;59(4):798–802.PubMed
66.
go back to reference Awakura Y et al. Methylation-associated silencing of TU3A in human cancers. Int J Oncol. 2008;33(4):893–9.PubMed Awakura Y et al. Methylation-associated silencing of TU3A in human cancers. Int J Oncol. 2008;33(4):893–9.PubMed
67.
go back to reference Kvasha S et al. Hypermethylation of the 5′CpG island of the FHIT gene in clear cell renal carcinomas. Cancer Lett. 2008;265(2):250–7.PubMedCrossRef Kvasha S et al. Hypermethylation of the 5′CpG island of the FHIT gene in clear cell renal carcinomas. Cancer Lett. 2008;265(2):250–7.PubMedCrossRef
68.
go back to reference Kawakami T et al. Imprinted DLK1 is a putative tumor suppressor gene and inactivated by epimutation at the region upstream of GTL2 in human renal cell carcinoma. Hum Mol Genet. 2006;15(6):821–30.PubMedCrossRef Kawakami T et al. Imprinted DLK1 is a putative tumor suppressor gene and inactivated by epimutation at the region upstream of GTL2 in human renal cell carcinoma. Hum Mol Genet. 2006;15(6):821–30.PubMedCrossRef
69.
70.
go back to reference Yano T et al. Tumor-suppressive effect of connexin 32 in renal cell carcinoma from maintenance hemodialysis patients. Kidney Int. 2003;63(1):381–1.PubMedCrossRef Yano T et al. Tumor-suppressive effect of connexin 32 in renal cell carcinoma from maintenance hemodialysis patients. Kidney Int. 2003;63(1):381–1.PubMedCrossRef
71.
go back to reference Yano T et al. Hypermethylation of the CpG island of connexin 32, a candiate tumor suppressor gene in renal cell carcinomas from hemodialysis patients. Cancer Lett. 2004;208(2):137–42.PubMedCrossRef Yano T et al. Hypermethylation of the CpG island of connexin 32, a candiate tumor suppressor gene in renal cell carcinomas from hemodialysis patients. Cancer Lett. 2004;208(2):137–42.PubMedCrossRef
72.
go back to reference Nojima D et al. CpG methylation of promoter region inactivates E-cadherin gene in renal cell carcinoma. Mol Carcinog. 2001;32(1):19–27.PubMedCrossRef Nojima D et al. CpG methylation of promoter region inactivates E-cadherin gene in renal cell carcinoma. Mol Carcinog. 2001;32(1):19–27.PubMedCrossRef
73.
go back to reference Yoo KH et al. Epigenetic inactivation of HOXA5 and MSH2 gene in clear cell renal cell carcinoma. Pathol Int. 2010;60(10):661–6.PubMedCrossRef Yoo KH et al. Epigenetic inactivation of HOXA5 and MSH2 gene in clear cell renal cell carcinoma. Pathol Int. 2010;60(10):661–6.PubMedCrossRef
74.
go back to reference Clifford SC et al. Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene and allelic losses at chromosome arm 3p in primary renal cell carcinoma: evidence for a VHL-independent pathway in clear cell renal tumourigenesis. Genes Chromosomes Cancer. 1998;22(3):200–9.PubMedCrossRef Clifford SC et al. Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene and allelic losses at chromosome arm 3p in primary renal cell carcinoma: evidence for a VHL-independent pathway in clear cell renal tumourigenesis. Genes Chromosomes Cancer. 1998;22(3):200–9.PubMedCrossRef
75.
go back to reference Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499(7456):43–9.CrossRef Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499(7456):43–9.CrossRef
76.
77.
go back to reference Yoo KH, Park YK, Chang SG. DNA hypomethylation of interleukin 8 in clear cell renal cell carcinoma. Oncol Lett. 2013;5(1):39–42.PubMedCentralPubMed Yoo KH, Park YK, Chang SG. DNA hypomethylation of interleukin 8 in clear cell renal cell carcinoma. Oncol Lett. 2013;5(1):39–42.PubMedCentralPubMed
78.
go back to reference Dunker K et al. Expression and regulation of non-classical HLA-G in renal cell carcinoma. Tissue Antigens. 2008;72(2):137–48.PubMedCrossRef Dunker K et al. Expression and regulation of non-classical HLA-G in renal cell carcinoma. Tissue Antigens. 2008;72(2):137–48.PubMedCrossRef
79.
go back to reference Cho M et al. Activation of the MN/CA9 gene is associated with hypomethylation in human renal cell carcinoma cell lines. Mol Carcinog. 2000;27(3):184–9.PubMedCrossRef Cho M et al. Activation of the MN/CA9 gene is associated with hypomethylation in human renal cell carcinoma cell lines. Mol Carcinog. 2000;27(3):184–9.PubMedCrossRef
80.
81.
go back to reference Hagiwara H et al. 5-Aza-2′-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene. Br J Pharmacol. 2008;153(7):1373–81.PubMedCentralPubMedCrossRef Hagiwara H et al. 5-Aza-2′-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene. Br J Pharmacol. 2008;153(7):1373–81.PubMedCentralPubMedCrossRef
83.
go back to reference Hu CY et al. Kidney cancer is characterized by aberrant methylation of tissue-specific enhancers that are prognostic for overall survival. Clin Cancer Res. 2014;20(16):4349–60.PubMedCrossRef Hu CY et al. Kidney cancer is characterized by aberrant methylation of tissue-specific enhancers that are prognostic for overall survival. Clin Cancer Res. 2014;20(16):4349–60.PubMedCrossRef
Metadata
Title
Role of DNA methylation in renal cell carcinoma
Authors
Niraj Shenoy
Nishanth Vallumsetla
Yiyu Zou
Jose Nahun Galeas
Makardhwaj Shrivastava
Caroline Hu
Katalin Susztak
Amit Verma
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2015
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-015-0180-y

Other articles of this Issue 1/2015

Journal of Hematology & Oncology 1/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine