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Medical Oncology

Erschienen in:

01.12.2011 | Original Paper

p14^ARF promoter region methylation as a marker for gliomas diagnosis

verfasst von: Jie He, Jian-bing Qiao, Haiqing Zhu

Erschienen in: Medical Oncology | Ausgabe 4/2011

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Abstract

Methylation in the promoter region is one of the mechanisms through which tumor suppressors are inactivated, resulting in tumorigenesis and/or tumor progression. Herein, we studied the methylation status in the promoter region of the p14^ARF tumor suppressor gene in 33 brain tissues isolated from glioma patients (astrocytomas) and compared to 12 brain tissues isolated from autopsy donors using methylation-specific polymerase chain reaction (MSP). The correlation between the expression of P14 and P53 was investigated using immunohistochemistry (IHC). The average percentage of methylation in the promoter region of p14^ARF gene in brain samples from glioma patients is 39.4%, while 0 from autopsy donors. No difference in the methylation level between low-grade and high-grade gliomas was detected. The methylation status has no correlation with the prognosis in glioma patients. A significant correlation between the expression of mutant form of TP53 and the grade of the glioma was established. Furthermore, there was a negative correlation between methylation of the p14^ARF promoter and the expression of the mutant form of TP53. Therefore, our data suggest that methylation in the promoter region of the p14^ARF gene may be used as a biomarker for the diagnosis of gliomas.

Loew S, Schmidt U, Unterberg A, Halatsch ME. The epidermal growth factor receptor as a therapeutic target in glioblastoma multiforme and other malignant neoplasms. Anticancer Agents Med Chem. 2009;9:703–15.PubMed

Ayuso-Sacido A, Moliterno JA, Kratovac S, Kapoor GS, O’Rourke DM, Holland EC, García-Verdugo JM, Roy NS, Boockvar JA. Activated EGFR signaling increases proliferation, survival, and migration and blocks neuronal differentiation in post-natal neural stem cells. J Neurooncol. 2010;97:323–37.PubMedCrossRef

Homma T, Fukushima T, Vaccarella S, Yonekawa Y, Di Patre PL, Franceschi S, Ohgaki H. Correlation among pathology, genotype, and patient outcomes in glioblastoma. J Neuropathol Exp Neurol. 2006;65:846–54.PubMedCrossRef

Ohgaki H, Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schüler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lütolf UM, Kleihues P. Genetic pathways to glioblastoma: a population-based study. Cancer Res. 2004;64:6892–9.PubMedCrossRef

Ohgaki H. Genetic pathways to glioblastomas. Neuropathology. 2005;25:1–7.PubMedCrossRef

Marko NF, Prayson RA, Barnett GH, Weil RJ. Integrated molecular analysis suggests a three-class model for low-grade gliomas: a proof-of-concept study. Genomics. 2010;95:16–24.PubMedCrossRef

Jeon YK, Park K, Park CK, Paek SH, Jung HW, Park SH. Chromosome 1p and 19q status and p53 and p16 expression patterns as prognostic indicators of oligodendroglial tumors: a clinicopathological study using fluorescence in situ hybridization. Neuropathology. 2007;27:10–20.PubMedCrossRef

Aldape K, Burger PC, Perry A. Clinicopathologic aspects of 1p/19q loss and the diagnosis of oligodendroglioma. Arch Pathol Lab Med. 2007;131:242–51.PubMed

Fontaine D, Vandenbos F, Lebrun C, Paquis V, Frenay M. Diagnostic and prognostic values of 1p and 19q deletions in adult gliomas: critical review of the literature and implications in daily clinical practice. Rev Neurol (Paris). 2008;164:595–604.CrossRef

10.

Elias A, Siegelin MD, Steinmüller A, von Deimling A, Lass U, Korn B, Mueller W. Epigenetic silencing of death receptor 4 mediates tumor necrosis factor-related apoptosis-inducing ligand resistance in gliomas. Clin Cancer Res. 2009;15:5457–65.PubMedCrossRef

11.

Nagarajan RP, Costello JF. Molecular epigenetics and genetics in neuro-oncology. Neurotherapeutics. 2009;6:436–46.PubMedCrossRef

12.

Chin L, Pomerantz J, DePinho RA. The INK4a/ARF tumor suppressor: one gene—two products—two pathways. Trends Biochem Sci. 1998;23:291–6.PubMedCrossRef

13.

Watanabe T, Katayama Y, Yoshino A, Yachi K, Ohta T, Ogino A, Komine C, Fukushima T. Aberrant hypermethylation of p14ARF and O6-methylguanine-DNA methyltransferase genes in astrocytoma progression. Brain Pathol. 2007;17:5–10.PubMedCrossRef

14.

Carr J, Bell E, Pearson AD, Kees UR, Beris H, Lunec J, Tweddle DA. Increased frequency of aberrations in the p53/MDM2/p14(ARF) pathway in neuroblastoma cell lines established at relapse. Cancer Res. 2006;66:2138–45.PubMedCrossRef

15.

Brooks CL, Gu W. Dynamics in the p53-Mdm2 ubiquitination pathway. Cell Cycle. 2004;3:895–9.PubMed

16.

Ohta S, Uemura H, Matsui Y, Ishiguro H, Fujinami K, Kondo K, Miyamoto H, Yazawa T, Danenberg K, Danenberg PV, Tohnai I, Kubota Y. Alterations of p16 and p14ARF genes and their 9p21 locus in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107:81–91.PubMedCrossRef

17.

Kim M, Yim SH, Cho NS, Kang SH, Ko DH, Oh B, Kim TY, Min HJ, She CJ, Kang HJ, Shin HY, Ahn HS, Yoon SS, Kim BK, Shin HR, Han KS, Cho HI, Lee DS. Homozygous deletion of CDKN2A (p16, p14) and CDKN2B (p15) genes is a poor prognostic factor in adult but not in childhood B-lineage acute lymphoblastic leukemia: a comparative deletion and hypermethylation study. Cancer Genet Cytogenet. 2009;195:59–65.PubMedCrossRef

18.

Kominami K, Nagasaka T, Cullings HM, Hoshizima N, Sasamoto H, Young J, Leggett BA, Tanaka N, Matsubara N. Methylation in p14(ARF) is frequently observed in colorectal cancer with low-level microsatellite instability. J Int Med Res. 2009;37:1038–45.PubMed

19.

Xiong J, Epstein RJ. Growth inhibition of human cancer cells by 5-aza-2′-deoxycytidine does not correlate with its effects on INK4a/ARF expression or initial promoter methylation status. Mol Cancer Ther. 2009;8:779–85.PubMedCrossRef

20.

Gonzlaez-Gomez P, Bello MJ, Arjona D, Lomas J, Alonso ME, De Campos JM, Vaquero J, Isla A, Gutierrez M, Rey JA. Promoter hypermethylation of multiple genes in astrocytic gliomas. Int J Oncology. 2003;22:601–8.

21.

Yu J, Zhang H, Gu J, Lin S, Li J, Lu W, Wang Y, Zhu J. Methylation profiles of thirty-four promoter-CpG islands and concordant methylation behaviours of sixteen genes that may contribute to carcinogenesis of astrocytoma. BMC Cancer. 2004;4:65–79.PubMedCrossRef

22.

Nosho K, Kawasaki T, Chan AT, Ohnishi M, Suemoto Y, Kirkner GJ, Fuchs CS, Ogino S. Cyclin D1 is frequently overexpressed in microsatellite unstable colorectal cancer, independent of CpG island methylator phenotype. Histopathology. 2008;53:588–98.PubMedCrossRef

23.

Ksiaa F, Ziadi S, Amara K, Korbi S, Trimeche M. Biological significance of promoter hypermethylation of tumor-related genes in patients with gastric carcinoma. Clin Chim Acta. 2009;404:128–33.PubMedCrossRef

24.

De Jong WK, Verpooten GF, Kramer H, Louwagie J, Groen HJ. Promoter methylation primarily occurs in tumor cells of patients with non-small cell lung cancer. Anticancer Res. 2009;29:363–9.PubMed

25.

Lin HH, Ke HL, Huang SP, Wu WJ, Chen YK, 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. 2009. doi:10.1016/j.urolonc.2008.12.008.

26.

Kuo LT, Kuo KT, Lee MJ, Wei CC, Scaravilli F, Tsai JC, Tseng HM, Kuo MF, Tu YK. Correlation among pathology, genetic and epigenetic profiles, and clinical outcome in oligodendroglial tumors. Int J Cancer. 2009;124:2872–9.PubMedCrossRef

27.

Santos MC, Saito CP, Line SR. Extraction of genomic DNA from paraffin-embedded tissue section of human fetuses fixed and stored in formalin for long periods. Pathol Res Pract. 2008;204:633–6.PubMedCrossRef

28.

Sato M, Horio Y, Sekido Y, Minna JD, Shimokata K, Hasegawa Y. The expression of DNA methyltransferases and methyl-CpG-binding proteins is not associated with the methylation status of p14(ARF), p16(INK4a) and RASSF1A in human lung cancer cell lines. Oncogene. 2002;21:4822–9.PubMedCrossRef

29.

Hamelin R, Laurent-Puig P, Olschwang S, Jego N, Asselain B, Remvikos Y, Girodet J, Salmon RJ, Thomas G. Association of p53 mutations with short survival in colorectal cancer. Gastroenterology. 1994;106:42–8.PubMed

30.

Winchester G. p53 protein and control of growth. Nature. 1983;303:660–1.PubMedCrossRef

31.

Oren M. The p53 cellular tumor antigen: gene structure, expression and protein properties. Biochim Biophys Acta. 1985;823:67–78.PubMed

32.

Lane DP, Benchimol S. p53: oncogene or anti-oncogene? Genes Dev. 1990;4:1–8.PubMedCrossRef

33.

Kondo I, Iida S, Takagi Y, Sugihara K. MDM2 mRNA expression in the p53 pathway may predict the potential of invasion and liver metastasis in colorectal cancer. Dis Colon Rectum. 2008;51:1395–402.PubMedCrossRef

34.

Pacifico A, Goldberg LH, Peris K, Chimenti S, Leone G, Ananthaswamy HN. Loss of CDKN2A and p14ARF expression occurs frequently in human monmelanoma skin cancers. Br J Dermatol. 2008;158:291–7.PubMedCrossRef

Titel: p14ARF promoter region methylation as a marker for gliomas diagnosis
verfasst von: Jie He
Jian-bing Qiao
Haiqing Zhu
Publikationsdatum: 01.12.2011
Verlag: Springer US
Erschienen in: Medical Oncology / Ausgabe 4/2011
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-010-9651-8

Springer Medizin

p14^ARF promoter region methylation as a marker for gliomas diagnosis

Abstract

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