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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'

emailnastad@vinca.rs
Project:
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
Abstract
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.
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article language: English
document type: Original Paper
DOI: 10.2478/jomb-2014-0009
published in SCIndeks: 13/11/2013

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