GATA5 CpG island hypermethylation is an independent predictor for poor clinical outcome in renal cell carcinoma

Peters,Inga; Gebauer,Kai; Dubrowinskaja,Natalia; Atschekzei,Faranaz; Kramer,Mario W.; Hennenlotter,Joerg; Tezval,Hossein; Abbas,Mahmoud; Scherer,Ralph; Merseburger,Axel S.; Stenzl,Arnulf; Kuczyk,Markus A.; Serth,Juergen

doi:10.3892/or.2014.3030

2014-April Volume 31 Issue 4

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2014-April Volume 31 Issue 4

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Article Open Access

GATA5 CpG island hypermethylation is an independent predictor for poor clinical outcome in renal cell carcinoma

Authors:
- Inga Peters
- Kai Gebauer
- Natalia Dubrowinskaja
- Faranaz Atschekzei
- Mario W. Kramer
- Joerg Hennenlotter
- Hossein Tezval
- Mahmoud Abbas
- Ralph Scherer
- Axel S. Merseburger
- Arnulf Stenzl
- Markus A. Kuczyk
- Juergen Serth
View Affiliations / Copyright

Affiliations: Department of Urology and Urologic Oncology, Hannover Medical School, D-30625 Hannover, Germany, Department of Urology, Eberhard-Karls University, D-72076 Tuebingen, Germany, Department of Pathology, Hannover Medical School, D-30625 Hannover, Germany, Department of Biometry, Hannover Medical School, D-30625 Hannover, Germany

Copyright: © Peters et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 1523-1530
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Published online on: February 18, 2014

https://doi.org/10.3892/or.2014.3030
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Abstract

Transcriptional inactivation and CpG island (CGI) methylation of GATA transcription factor family members GATA3 and GATA5 have been reported for a few types of human cancer. Whether high-density CGI methylation of GATA3 or GATA5 is associated with the clinical course of patients with renal cell cancer (RCC) has not been clarified. Quantitative methylation-specific PCR assays were carried out to analyze 25 tumor cell lines including 6 RCC lines and 119 RCC and 87 adjacent normal tissues for the presence of densely methylated sequences. Methylation values were statistically compared with clinicopathological and recurrence-free survival (RFS) data for patients. Comparison of GATA3 and GATA5 methylation in different tumor cell lines revealed a marker-specific methylation characteristic with high and frequent signals for both methylation marks in RCC lines. GATA3 and GATA5 CGI relative methylation levels were found to be strongly associated with the state of metastasis (P=0.003 and P<0.001, respectively) and advanced disease (P=0.024 and P<0.001, respectively). Moreover, an independent decrease in RFS in Cox proportional hazard analysis was found for tumors exhibiting high GATA5 methylation (P<0.001, hazard ratio, 19.3; 95% confidence interval, 4.58-81.6). Epigenetic alterations in GATA family members may be associated with aggressive tumor phenotypes in RCC, and in the case of GATA5, may serve as a new independent molecular marker for aggressiveness and disease progression.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
2	Ljungberg B: Prognostic factors in renal cell carcinoma. Urologe A. 43(Suppl 3): S119–S120. 2004. View Article : Google Scholar : PubMed/NCBI
3	Kaelin WG Jr: The von Hippel-Lindau tumor suppressor gene and kidney cancer. Clin Cancer Res. 10:6290S–6295S. 2004. View Article : Google Scholar : PubMed/NCBI
4	Feinberg AP, Ohlsson R and Henikoff S: The epigenetic progenitor origin of human cancer. Nat Rev Genet. 7:21–33. 2006. View Article : Google Scholar : PubMed/NCBI
5	Dahl E, Wiesmann F, Woenckhaus M, et al: Frequent loss of SFRP1 expression in multiple human solid tumours: association with aberrant promoter methylation in renal cell carcinoma. Oncogene. 26:5680–5691. 2007. View Article : Google Scholar : PubMed/NCBI
6	Morris MR, Ricketts C, Gentle D, et al: Identification of candidate tumour suppressor genes frequently methylated in renal cell carcinoma. Oncogene. 29:2104–2117. 2010. View Article : Google Scholar : PubMed/NCBI
7	Peters I, Rehmet K, Wilke N, et al: RASSF1A promoter methylation and expression analysis in normal and neoplastic kidney indicates a role in early tumorigenesis. Mol Cancer. 6:492007. View Article : Google Scholar : PubMed/NCBI
8	Morris MR, Ricketts CJ, Gentle D, et al: Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. Oncogene. 30:1390–1401. 2011. View Article : Google Scholar
9	Ricketts CJ, Morris MR, Gentle D, et al: Genome-wide CpG island methylation analysis implicates novel genes in the pathogenesis of renal cell carcinoma. Epigenetics. 7:278–290. 2012. View Article : Google Scholar : PubMed/NCBI
10	Atschekzei F, Hennenlotter J, Janisch S, et al: SFRP1 CpG island methylation locus is associated with renal cell cancer susceptibility and disease recurrence. Epigenetics. 7:447–457. 2012. View Article : Google Scholar
11	van Vlodrop IJ, Baldewijns MM, Smits KM, et al: Prognostic significance of Gremlin1 (GREM1) promoter CpG island hypermethylation in clear cell renal cell carcinoma. Am J Pathol. 176:575–584. 2010.
12	Kent WJ, Sugnet CW, Furey TS, et al: The human genome browser at UCSC. Genome Res. 12:996–1006. 2002. View Article : Google Scholar : PubMed/NCBI
13	Patient RK and McGhee JD: The GATA family (vertebrates and invertebrates). Curr Opin Genet Dev. 12:416–422. 2002. View Article : Google Scholar : PubMed/NCBI
14	Chou J, Provot S and Werb Z: GATA3 in development and cancer differentiation: cells GATA have it! J Cell Physiol. 222:42–49. 2010.
15	Abba MC, Nunez MI, Colussi AG, Croce MV, Segal-Eiras A and Aldaz CM: GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells. Breast Cancer Res. 8:R642006. View Article : Google Scholar : PubMed/NCBI
16	Tavares TS, Nanus D, Yang XJ and Gudas LJ: Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 7:1607–1618. 2008. View Article : Google Scholar : PubMed/NCBI
17	Gebauer K, Peters I, Dubrowinskaja N, et al: Hsa-mir-124–3 CpG island methylation is associated with advanced tumours and disease recurrence of patients with clear cell renal cell carcinoma. Br J Cancer. 108:131–138. 2013.
18	Sobin LH and Compton CC: TNM seventh edition: what’s new, what’s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer. 116:5336–5339. 2010.
19	Thoenes W and Storkel S: Pathology of benign and malignant renal cell tumors. Urologe A. 30:W41–W50. 1991.(In German).
20	Peters I, Eggers H, Atschekzei F, et al: GATA5 CpG island methylation in renal cell cancer: a potential biomarker for metastasis and disease progression. BJU Int. 110:E144–E152. 2012. View Article : Google Scholar
21	Weisenberger DJ, Siegmund KD, Campan M, et al: CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 38:787–793. 2006. View Article : Google Scholar
22	Lander ES, Linton LM, Birren B, et al: Initial sequencing and analysis of the human genome. Nature. 409:860–921. 2001. View Article : Google Scholar : PubMed/NCBI
23	Weisenberger DJ, Campan M, Long TI, et al: Analysis of repetitive element DNA methylation by MethyLight. Nucleic Acids Res. 33:6823–6836. 2005. View Article : Google Scholar : PubMed/NCBI
24	Graf T and Enver T: Forcing cells to change lineages. Nature. 462:587–594. 2009. View Article : Google Scholar : PubMed/NCBI
25	Cooper SJ, Zou H, Legrand SN, et al: Loss of type III transforming growth factor-β receptor expression is due to methylation silencing of the transcription factor GATA3 in renal cell carcinoma. Oncogene. 29:2905–2915. 2010.
26	Yamada D, Kikuchi S, Williams YN, et al: Promoter hypermethylation of the potential tumor suppressor DAL-1/4.1B gene in renal clear cell carcinoma. Int J Cancer. 118:916–923. 2006. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

GATA5 CpG island hypermethylation is an independent predictor for poor clinical outcome in renal cell carcinoma

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