TP53 and C-MYC Co-Alterations – A Hallmark of Oral Cancer Progression / SIMULTANA ALTERACIJA TP53 I C-MYC GENA – OBELEŽJE PROGRESIJE ORALNIH KARCINOMA

Abstract

Summary 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. There- fore, reliable molecular markers for oral cancer progression are badly needed. Methods: We conducted a copy number analysis to esti- mate amplification status of c-myc, cycD1 and EGFR onco- genes, mutational PCR-SSCP analysis to determine activa- tion of H-ras oncogene and inactivation of TP55 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%, cycD1 in 20% and EGFR in 16.7% of Oral Squamous Cell Carci- noma (OSCC) cases while H-ras was activated in 33.3% of samples. Amplification of c-myc was significantly associat- ed 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 cycD1 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, TP55 and c-myc oncogene were simultaneously altered in grade 2 OSCC. Conclusions: The most promising marker of OSCC pro- gression remains the TP53 tumour suppressor, which is the most frequently mutated gene in oral cancers. Since there is synergism between TP55 and c-myc, it seems that co- alteration of these two genes could be also a good marker of OSCC progression from gradel to grade 2 tumours.