VHL, PBRM1 and SETD2 Genes in Kidney Cancer: A Molecular Investigation
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.
[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.
[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.
@article{"International Journal of Medical, Medicine and Health Sciences:70003", author = "Rozhgar A. Khailany and Mehri Igci and Emine Bayraktar and Sakip Erturhan and Metin Karakok and Ahmet Arslan", title = "VHL, PBRM1 and SETD2 Genes in Kidney Cancer: A Molecular Investigation", 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.", volume = "9", number = "5", pages = "423-4", }
