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VHL, PBRM1 and SETD2 Genes in Kidney Cancer: A Molecular Investigation

Authors: Rozhgar A. Khailany, Mehri Igci, Emine Bayraktar, Sakip Erturhan, Metin Karakok, Ahmet Arslan

Abstract:

Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p>0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Keywords: Kidney cancer, molecular biomarker, expression analysis, mutation screening.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1106329

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References:


[1] M.S. Litwin, Urologic diseases in America, 1st ed, Washington, U.S.A.: 2007, ch. 2. , pp. 337- 341.
[2] K. Junker, V. Ficarra, E.D. Kwon, , B.C. Leibovich, R.H.Thompson, and E. Oosterwijk, “potential role of genetic markers in the management of kidney cancer,” European Urology. vol. 63, pp. 333–340, 2013.
[3] Oncology, 2 nd ed, J. Cassidy, D. Bisset, R.A.J. Spence, and M. Payne, 2006, New York, pp. 30-31.
[4] K. Stemmer, “Molecular characteristics of kidney cancer,” Ph.D. dissertation, Dept. Biology, der Konstanz Uni, 2008.
[5] Q. Yin-Goen, J. Dale, W.L. Yang, J. Phan, R. Moffitt, J.A. Petros, M.W. Datta, M.B. Amin, M.D. Wang, and A.N. Young, “Advances in molecular classification of renal neoplasms,” HistolHistopathol. Vol. 21, no. 3, pp. 325-39, 2006.
[6] V. Kumar, K. Abul, N. Fausto, R. Mitchell, Basic Pathology, 2007, PP. 271- 272.
[7] S. Pelengaris, and M. Khan, (2013) The molecular biology of cancer, ch. 10, pp. 5-10.
[8] M. Rajer “Kidney cancer ,” Radiol Oncol, vol. 41, pp. 64-71, 2007.
[9] B. Perroud, N. Valkova, A. Dhirapong, L. Fiehn, D. Kültz, R.H. Weiss, (2006) “Pathway analysis of kidney cancer using proteomics and metabolic profiling”. BioMed Central, PP. 1-17, 2006.
[10] L.L. Darwin, E. Stephen, F. Pautler, “Current understanding of the molecular mechanisms of kidney cancer: a primer for urologists” Canadian Urological Association, vol. 1, pp. 12 – 20, 2007.
[11] J. Leslie, K. Furge, B.T. Teh (2012) “Renal Cell Carcinoma Deep Sequencing Recent Developments” CurrOncol Rep, vol. 14, pp. 240– 248, 2012.
[12] R. Kiyama, Y. Zhu, and T. Aoyagi, Renal Tumor, 3rd ed, pp. 3 – 7, 2013.
[13] M. Dandanell, L. Sunde, F.C. Nielsen, and T. V. Hansen “Identification of three novel VHL germ-line mutations in Danish VHL patients” BMC Medical Genetics, vol. 13. pp. 1–6, 2012.
[14] Y. Lai, K. Hakal, T. Susan, and Y. Shiio “Proteomic dissection of the VHL interactome” NIH Public Access, vol. 11, no. 10, pp. 5175–5182, 2011.
[15] A. Hakimi, J. Wren, M. Gonen, and O. Abdel-Wahab “Clinical and Pathologic Impact of Select Chromatin Modulating Tumor Suppressors in Clear Cell Renal Cell Carcinoma” NIH Public Access, vol. 63, no. 5, pp. 848–854, 2012.
[16] https://www.google.iq/#q=genetic+home+reference.
[17] http://www.genecards.org/cgi-bin/carddisp.pl?gene 03-08-2012 14:30.
[18] I. Varela, K. Raine, D. Huang, C. K. Ong, and P. Stephens (2011) “Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma” Nature, vol. 469, pp. 539– 542, 2011.
[19] P. Xie, C. Tian, J. Nie, K. Lu, G. Xing, L. Zhang, and H. Fuchu “Histone methyltransferase protein SETD2 interacts with p53 and selectively regulates its downstream genes” Science direct, vol. 20. pp. 1671–1678, 2008.
[20] M. Yao, T. Kishida, N. Nakaigawa, and M. Baba “VHL Tumor Suppressor Gene Alterations Associated With Good Prognosis in Sporadic Clear-Cell Renal Carcinoma”. Journal of the National Cancer Institute, vol. 94, pp. 1569–1575, 2002.
[21] R. Henrique, A. Silvia, and C. Jeronimo “The epigenetics of renal cell tumors: from biology to biomarkers” Frontiers genetic, vol. 3, pp. 1–13, 2012.
[22] L. Gillian, C. Greenman, and L. Chen. “Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes” Nature, vol. 463, pp. 360 – 363, 2012.
[23] E. Cherkasova, E. Malinzak, S. Rao, and Y. Takahashi “Inactivation of the von Hippel-Lindau tumor suppressor leads to selective expression of a human endogenous retrovirus in kidney cancer” NIH Public Access, vol. 47, no. 30, pp. 4697–4706, 2011.
[24] Y. Z. Igci, A. Arslan, E. Akarsu, S. Erkilic, M. Igci, S. Oztuzcu, B. Cengiz, B. Gogebakan, E. A. Cakmak, and A. T. Demiryurek “Differential Expression of a Set of Genes in Follicular and Classic Variants of Papillary Thyroid Carcinoma” Endocr Pathol, vol. 2, no. 22, pp. 86-96, Jun 2011.