Genetic alterations of chromosomes, p53 and p16 genes in low- and high-grade bladder cancer

Abat,Deniz; Demirhan,Osman; Inandiklioglu,Nihal; Tunc,Erdal; Erdogan,Seyda; Tastemir,Deniz; Uslu,Inayet  Nur; Tansug,Zuhtu

doi:10.3892/ol.2014.2108

Genetic alterations of chromosomes, p53 and p16 genes in low- and high-grade bladder cancer

Authors:
- Deniz Abat
- Osman Demirhan
- Nihal Inandiklioglu
- Erdal Tunc
- Seyda Erdogan
- Deniz Tastemir
- Inayet Nur Uslu
- Zuhtu Tansug
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Affiliations: Department of Urology, Faculty of Medicine, Çukurova University, 01330 Adana, Turkey, Department of Medical Biology, Faculty of Medicine, Çukurova University, 01330 Adana, Turkey, Department of Pathology, Faculty of Medicine, Çukurova University, 01330 Adana, Turkey, Vocational School of Health Services, Adıyaman University, 02040 Adıyaman, Turkey
Published online on: May 2, 2014 https://doi.org/10.3892/ol.2014.2108
Pages: 25-32

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Abstract

A majority of patients with bladder cancer present with superficial disease and subsequently, some patients show progression to muscle invasive or metastatic disease. Bladder cancer has a complex genetic process and identification of the genetic alterations which occur during progression may lead to the understanding of the nature of the disease and provide the possibility of early treatment. The aim of the present study was to compare the structural and numerical chromosomal differences and changes in the p16 and p53 genes between low‑grade (LG) and high‑grade (HG) bladder cancer (BC) using cytogenetic and molecular cytogenetic methods. Between March 2009 and March 2010, cytogenetic analyses were carried out on tumor and blood samples in 34 patients with transitional cell type BC, and on blood samples of 34 healthy patients as a control group. Fluorescence in situ hybridization probes for the p16 and p53 genes were also used to screen the alterations in these genes in 32 patients with BC. The patients were divided into two groups (LG and HG) and the findings were compared. A total of 11 (32.3%) patients exhibited LGBC, 22 (64.7%) exhibited HGBC and one (3%) patient exhibited carcinoma in situ. There were no differences between the LGBC and HGBC groups according to the number of chromosomal aberrations (P=0.714); however, differences between alterations of the p16 and p53 genes were significant (P=0.002 and P=0.039). Almost all structural abnormalities were found to be located to the 1q21, 1q32, 3p21 and 5q31 regions in patients with HG tumors. In conclusion, the p16 and p53 genes were altered more prominently in patients with HG tumors compared with LG tumors. The structural abnormalities in the 1q21, 1q32, 3p21 and 5q31 regions were observed more frequently in patients with HG tumors. These regions may play significant roles in the progression of BC, but further studies are required to find candidate genes for a panel of BC.

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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.
2	Jacobs BL, Lee CT and Montie JE: Bladder cancer in 2010: how far have we come? CA Cancer J Clin. 60:244–272. 2010.
3	Sullivan PS, Chan JB, Levin MR and Rao J: Urine cytology and adjunct markers for detection and surveillance of bladder cancer. Am J Trans Res. 2:412–440. 2010.
4	Vrooman OP and Witjes JA: Molecular markers for detection, surveillance and prognostication of bladder cancer. Int J Urol. 16:234–243. 2009.
5	Habuchi T, Marberger M, Droller MJ, et al: Prognostic markers for bladder cancer: International Consensus Panel on bladder tumor markers. Urology. 66(Suppl 1): 64–74. 2005.
6	Proctor I, Stoeber K and Williams GH: Biomarkers in bladder cancer. Histopathology. 57:1–13. 2010.
7	Lin HH, Ke HL, Huang SP, Wu WJ, Chen YK and Chang LL: Increase sensitivity in detecting superficial, low grade bladder cancer by combination analysis of hypermethylation of E-cadherin, p16, p14, RASSF1A genes in urine. Urol Oncol. 28:597–602. 2010.
8	Knowles MA: The genetics of transitional cell carcinoma: progress and potential clinical application. BJU Int. 84:412–427. 1999.
9	Cianciulli AM, Leonardo C, Guadagni F, et al: Genetic instability in superficial bladder cancer and adjacent mucosa: an interphase cytogenetic study. Hum Pathol. 34:214–221. 2003.
10	Eble JN, Sauter G, Epstein JI and Sesterhenn I: WHO Classification of Tumours Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. IARC Press; Lyon: pp. 90–91. 2004
11	Fundia AF and Larripa IB: Coincidence in fragile site expression with fluorodeoxyuridine and bromodeoxyuridine. Cancer Genet Cytogenet. 41:41–48. 1989.
12	Mitelman F: ISCN: An International System for Human Cytogenetics Nomenclature. S Karger; Basel: 1995
13	McAlpine PJ, Shows TB, Boucheli C, Huebner M and Anderson WA: The 1991 catalog of mapped genes and report of the nomenclature committee, Human Gene Mapping 11. Cytogenet Cell Genet. 58:5–102. 1991.
14	Trask B and Pinkel D: Fluorescence in situ hybridization with DNA probes. Methods Cell Biol. 33:383–400. 1990.
15	Junker K, van Oers JM, Zwarthoff EC, Kania I, Schubert J and Hartmann A: Fibroblast growth factor receptor 3 mutations in bladder tumors correlate with low frequency of chromosome alterations. Neoplasia. 10:1–7. 2008.
16	Wolff DJ: The genetics of bladder cancer: a cytogeneticist’s perspective. Cytogenet Genome Res. 118:177–181. 2007.
17	Tommasi S, Dammann R, Jin SG, Zhang XF, Avruch J and Pfeifer GP: RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1. Oncogene. 18: 21:2713–2720. 2002.
18	Caramazza D, Hussein K, Siragusa S, et al: Chromosome 1 abnormalities in myeloid malignancies: a literature survey and karyotype-phenotype associations. Eur J Haematol. 84:191–200. 2010.
19	Ichimura Y, Habuchi T, Tsuchiya N, et al: Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant. J Urol. 172:728–732. 2004.
20	Awakura Y, Nakamura E, Ito N, Kamoto T and Ogawa O: Methylation-associated silencing of TU3A in human cancers. Int J Oncol. 33:893–899. 2008.
21	Duns G, van den Berg E, van Duivenbode I, et al: Histone methyltransferase gene SETD2 is a novel tumor suppressor gene in clear cell renal cell carcinoma. Cancer Res. 1: 70:4287–4291. 2010.
22	Angeloni D: Molecular analysis of deletions in human chromosome 3p21 and the role of resident cancer genes in disease. Brief Funct Genomic Proteomic. 6:19–39. 2007.
23	Jarmalaite S, Jankevicius F, Kurgonaite K, Suziedelis K, Mutanen P and Husgafvel-Pursiainen K: Promoter hypermethylation in tumour suppressor genes shows association with stage, grade and invasiveness of bladder cancer. Oncology. 75:145–151. 2008.
24	Dammann R, Schagdarsurengin U, Seidel C, et al: The tumor suppressor RASSF1A in human carcinogenesis: an update. Histol Histopathol. 20:645–663. 2005.
25	Dallosso AR, Hancock AL, Szemes M, et al: Frequent long-range epigenetic silencing of protocadherin gene clusters on chromosome 5q31 in Wilms’ tumor. PLoS Genet. 5:10007452009.
26	Kanetsky PA, Mitra N, Vardhanabhuti S, et al: Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer. Nat Genet. 41:811–815. 2009.
27	Nakazawa K, Murata S, Yuminamochi T, et al: p16(INK4a) expression analysis as an ancillary tool for cytologic diagnosis of urothelial carcinoma. Am J Clin Pathol. 132:776–784. 2009.
28	Chang LL, Yeh WT, Yang SY, Wu WJ and Huang CH: Genetic alterations of p16INK4a and p14ARF genes in human bladder cancer. J Urol. 170:595–600. 2003.
29	Krüger S, Mahnken A, Kausch I and Feller AC: P16 immunoreactivity is an independent predictor of tumor progression in minimally invasive urothelial bladder carcinoma. Eur Urol. 47:463–467. 2005.
30	Moonen PM, van Balken-Ory B, Kiemeney LA, Schalken JA and Witjes JA: Prognostic value of p53 for high risk superficial bladder cancer with long-term followup. J Urol. 177:80–83. 2007.
31	Smith ND, Rubenstein JN, Eggener SE and Kozlowski JM: The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the management of bladder cancer. J Urol. 169:1219–1228. 2003.
32	Malats N, Bustos A, Nascimento CM, et al: P53 as a prognostic marker for bladder cancer: a meta-analysis and review. Lancet Oncol. 6:678–686. 2005.
33	Shariat SF, Chade DC, Karakiewicz PI, et al: Combination of multiple molecular markers can improve prognostication in patients with locally advanced and lymph node positive bladder cancer. J Urol. 183:68–75. 2010.