Abstract
Epigenetic modifications have been recognized as an important mechanism underlying carcinoma progression. DNA methylation plays an important role in cancer biology and represents potentially heritable changes in gene expression that do not involve DNA sequence. The aim of this study was to investigate promoter methylation of selected genes in sinonasal carcinoma by comparison with noncancerous sinonasal tissue. To search for epigenetic events (methylation in 25 tumor suppressor genes) we used MS-MLPA (Methylation-specific multiplex ligation-dependent probe amplification) to compare methylation status of 59 formalin fixed, paraffin embedded tissue samples of sinonasal carcinomas with 18 control samples. The most important changes in methylation were confirmed using MSP (Methylation specific PCR). Detected alterations in methylation were compared with clinicopathological characteristics. Using a 20% cut-off for methylation (MS-MLPA), we found significantly higher methylation in GATA5 (P=0.0005), THSB1 (P=0.0002) and PAX5 (P=0.03) genes in the sinonasal cancer group compared to the control group. Methylation in five or more genes was associated with impaired overall survival (P=0.017). These findings provide evidence that alterations in methylation profile may be one of the major mechanisms in sinonasal carcinogenesis. In addition, changes in methylation could potentially be used as prognostic factors of sinonasal carcinoma and may have implications for future individualized therapy based on epigenetic changes.
Highlights
Malignant tumors of the sinonasal tract are rare tumors of the head and neck area that account for approximately 3% to 5% of all upper respiratory tract malignancies[1]
Using a 20% cut-off for methylation (MS-MLPA), we observed significantly higher methylation in GATA5 (P=0.0005), THBS1 (P=0.0002) and PAX5 (P=0.03) genes in the sinonasal cancer group compared to the control noncancerous group
Using Methylation-specific polymerase chain reaction (MSP) we weren’t able to confirm the presence of methylation of THSB1 gene in cancer samples, but it could be the result of the assay strategy (6 CpGs in primers, compared to 2 CpG restriction sites in Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) probe)
Summary
Malignant tumors of the sinonasal tract are rare tumors of the head and neck area that account for approximately 3% to 5% of all upper respiratory tract malignancies[1]. Diagnosis and treatment of these tumors pose several problems due to their very low incidence, histological diversity and production of non-specific symptoms in the early stages that can closely mimic inflammatory conditions. Their prognosis largely depends on histology, location and staging[6]. To search for epigenetic events (methylation in 25 tumor suppressor genes) we used MS–MLPA (Methylationspecific multiplex ligation-dependent probe amplification) to compare methylation status of 59 formalin fixed, paraffin embedded tissue samples of sinonasal carcinomas with 18 control samples. Changes in methylation could potentially be used as prognostic factors of sinonasal carcinoma and may have implications for future individualized therapy based on epigenetic changes
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