• citations in SCIndeks: [1]
  • citations in CrossRef:0
  • citations in Google Scholar:[]
  • visits in previous 30 days:18
  • full-text downloads in 30 days:3


article: 3 from 14  
Back back to result list
2013, vol. 32, iss. 4, pp. 380-388
TP53 and c-myc Co-alterations: A hallmark of oral cancer progression
aUniversity of Belgrade, Institute of Nuclear Sciences 'Vinča', Belgrade-Vinča
bUniversity of Belgrade, Faculty of Dental Medicine
cUniversity of Belgrade, Faculty of Dental Medicine, Department of Maxillofacial Surgery
dUniversity of Belgrade, Institute for Biological Research 'Siniša Stanković'
Identification of predictive molecular markers for cancer progression, response to therapy and disease outcome (MESTD - 41031)
Molecular determinants for tumor marker design (MESTD - 173049)

Keywords: c-myc; oncogenes; oral squamous cell carcinoma; TP53; tumour progression; tumour suppressors
Background: Head and neck squamous cell carcinoma, including oral cancer, is the sixth most common cancer worldwide. Despite advances in surgery and treatment, the 5-year survival rate has not improved significantly. Therefore, reliable molecular markers for oral cancer progression are badly needed. Methods: We conducted a copy number analysis to estimate amplification status of c-myc, cycD1 and EGFR oncogenes, mutational PCR-SSCP analysis to determine activation of H-ras oncogene and inactivation of TP53 tumour suppressor gene and methylation specific PCR analysis to evaluate hypermethylation of p16 and MGMT genes. Results: c-myc oncogene was amplified in 56.7%, cycDI in 20% and EGFR in 16.7% of Oral Squamous Cell Carcinoma (OSCC) cases while H-ras was activated in 33.3% of samples. Amplification of c-myc was significantly associated with the tumour grade 2. Interestingly, EGFR and H-ras alterations were mutually exclusive. p16 and MGMT were inactivated by hypermethylation in 30% and 13.3% of cases. Co-alteration of cycDI and p16 were not observed in any of the analyzed samples. TP53 was inactivated in 56.7% of samples and was significantly associated with progression of OSCC, grade 2 and stage 2. Moreover, TP53 and c-myc oncogene were simultaneously altered in grade 2 OSCC. Conclusions: The most promising marker of OSCC progression remains the TP53 tumour suppressor, which is the most frequently mutated gene in oral cancers. Since there is synergism between TP53 and c-myc, it seems that co-alteration of these two genes could be also a good marker of OSCC progression from grade1 to grade 2 tumours.
Akervall, J., Bockmuhl, U., Petersen, I., Yang, K., Thomas, E., Carey, T.E., i dr. (2003) The Gene Ratios c-MYC: Cyclin-dependent Kinase (CDK)N2A and CCND1: CDKN2A Correlate with Poor Prognosis in Squamous Cell Carcinoma of the Head and Neck. Clin Cancer Res, 9: 1750-5
Albanese, C., Johnson, J., Watanabe, G., Eklund, N., Vu, D., Arnold, A., Pestell, R.G. (1995) Transforming p21ras mutants and c-Ets-2 activate the cyclin D1 promoter through distinguishable regions. Journal of biological chemistry, 270(40): 23589-97
Amati, B., Alevizopoulos, K., Vlach, J. (1998) Myc and the cell cycle. Front Biosci, 3: d250-68
Bettendorf, O., Piffkò, J., Bànkfalvi, A. (2004) Prognostic and predictive factors in oral squamous cell cancer: important tools for planning individual therapy?. Oral oncology, 40(2): 110-9
Bitzer, M., Stahl, M., Arjumand, J., Rees, M., Klump, B., Heep, H., Gabbert, H.E., Sarbia, M. (2003) C-myc gene amplification in different stages of oesophageal squamous cell carcinoma: prognostic value in relation to treatment modality. Anticancer research, 23(2B): 1489-93
Callender, T., el-Naggar A.K., Lee, M.S., Frankenthaler, R., Luna, M.A., Batsakis, J.G. (1994) PRAD-1 (CCND1)/cyclin D1 oncogene amplification in primary head and neck squamous cell carcinoma. Cancer, 74(1): 152-8
Campo-Trapero, J., Cano-Sánchez, J., Palacios-Sánchez, B., Sánchez-Gutierrez, J.J., González-Moles, M.A., Bascones-Martínez, A. (2008) Update on molecular pathology in oral cancer and precancer. Anticancer research, 28(2B): 1197-205
Filipe, I.D., Marcia, F., da Rocha, H.R., Martha, C.M., Soares, Y.L. (2010) Main molecular markers of oral squamous cell carcinoma. Applied Cancer Research, 30, 279-88
Forastiere, A., Koch, W., Trotti, A., Sidransky, D. (2001) Head and neck cancer. New England journal of medicine, 345(26): 1890-900
Friedlander, P.L. (2001) Genomic instability in head and neck cancer patients. Head & neck, 23(8): 683-91
Herman, J.G., Graff, J.R., Myöhänen, S., Nelkin, B.D., Baylin, S.B. (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proceedings of the National Academy of Sciences of the United States of America, 93(18): 9821-6
Hussein, M.R., Cullen, K. (2001) Molecular biomarkers in HNSCC: prognostic and therapeutic implications. Expert review of anticancer therapy, 1(1): 116-24
Kim, M.M., Califano, J.A. (2004) Molecular pathology of head-and-neck cancer. International Journal of Cancer, 112(4): 545-53
Kuo, M.Y.P., Jeng, J.H., Chiang, C.P., Hahn, L.J. (1994) Mutations of Ki-ras oncogene codon 12 in betel quid chewing-related human oral squamous cell carcinoma in Taiwan. Journal of Oral Pathology and Medicine, 23(2): 70-74
Livak, K.J., Schmittgen, T.D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, Calif.), 25(4): 402-8
Loro, L.L., Vintermyr, O.K., Johannessen, A.C. (2003) Cell death regulation in oral squamous cell carcinoma: methodological considerations and clinical significance. Journal of oral pathology & medicine, 32(3): 125-38
Lowe, S.W., Lin, A.W. (2000) Apoptosis in cancer. Carcinogenesis, 21(3): 485-95
Mori, K., Hirao, E., Toya, Y., Oshima, Y., Ishikawa, F., Nose, K., Shibanuma, M. (2009) Competitive nuclear export of cyclin D1 and Hic-5 regulates anchorage dependence of cell growth and survival. Molecular biology of the cell, 20(1): 218-32
Musgrove, E.A. (2006) Cyclins: Roles in mitogenic signaling and oncogenic transformation. Growth Factors, 24(1): 13-19
Neville, B.W., Day, T.A. (2002) Oral cancer and precancerous lesions. CA: a cancer journal for clinicians, 52(4): 195-215
Orita, M., Iwahana, H., Kanazawa, H., Hayashi, K., Sekiya, T. (1989) Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proceedings of the National Academy of Sciences of the United States of America, 86(8): 2766-70
Papakosta, V., Vairaktaris, E., Vylliotis, A., Derka, S., Nkenke, E., Vassiliou, S., Lazaris, A., Mourouzis, C., Rallis, G., Spyridonidou, S., Anagnostopoulou, S., Perrea, D., Donta, I. (2006) The co-expression of c-myc and p53 increases and reaches a plateau early in oral oncogenesis. Anticancer research, 26(4B): 2957-62
Pisani, P., Bray, F., Parkin, M.D. (2002) Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. International Journal of Cancer, 97(1): 72-81
Popović, B., Jekić, B., Novaković, I., Luković, L., Konstantinović, V., Babić, M., Milasin, J. (2010) Cancer genes alterations and HPV infection in oral squamous cell carcinoma. International journal of oral and maxillofacial surgery, 39(9): 909-15
Sambrook, J., Fritsch, E.F., Maniatis, T., ur. (1989) Molecular cloning: A laboratory manual. New York: Cold Spring Harbor Laboratory Press
Silverman, S.Jr. (2001) Demographics and occurrence of oral and oropharyngeal cancers. The outcomes, the trends, the challenge. J Am Dent Assoc, 132: 75-115
Todd, R., Donoff, R.B., Wong, D.T. (1997) The molecular biology of oral carcinogenesis: toward a tumor progression model. Journal of oral and maxillofacial surgery, 55(6): 613-23; discussion 623-5
Tsantoulis, P.K., Kastrinakis, N.G., Tourvas, A.D., Laskaris, G., Gorgoulis, V.G. (2007) Advances in the biology of oral cancer. Oral Oncology, 43(6): 523-534
Wang, C., Lisanti, M.P., Liao, J.D. (2011) Reviewing once more the c-myc and Ras collaboration: converging at the cyclin D1-CDK4 complex and challenging basic concepts of cancer biology. Cell cycle (Georgetown, Tex.), 10(1): 57-67
Williams, H.K. (2000) Molecular pathogenesis of oral squamous carcinoma. Molecular pathology, 53(4): 165-72
Zheng, J., Li, W., Huang, R. (2000) Studies on c-myc gene expression and p16 gene inactivation in nasopharyngeal carcinoma. Zhonghua er bi yan hou ke za zhi, 35(6): 464-8


article language: English
document type: Original Paper
DOI: 10.2478/jomb-2014-0009
published in SCIndeks: 13/11/2013

Related records

No related records