Article
Promotermethylation of three new tumor suppressor genes in HNSCC and their precursor lesions
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Published: | September 7, 2006 |
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Outline
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Aim: Promoter methylation is an epigenetic mechanism resulting in loss of protein expression despite intakt gene. Recent studies demonstrate an inactivation of three new tumor suppressor genes (Semaphorin 3B (SEMA3B), BLU and RASSF1, located on 3p21, due to methylation of their promoter. We examined the role of methylation of the three abovementioned genes in the carcinogenesis of squamous cell carcinomas of the head and neck (HNSCC).
Material and methods: Promoter methylation of SEMA3B, BLU, RASSF1 was examined by MSP PCR in 95 HNSCC, 21 lowgrade and 16 highgrade intraepithelial neoplasias. Semiquantitative m- RNA expression was examined by RT- PCR.
Results: SEMA3B promoter methylation was present in 12/95 HNSCC and in none of the neoplasias. BLU was methylated in 29% of the carcinomas and in 18% and 9% of highgrade and lowgrade neoplasias, respectively. The promoter of RASSF1 was methylated in 19% of the carcinomas, 12% of high grade and 5% of low grade intraepithelial neoplasias. M-RNA expression of SEMA3B, BLU and RASSF1 was reduced in samples with promoter methylation.
Conclusion: Our results demomstrate that methylation of SEMA3B, BLU and RASSF1 does not play a major role in carcinogenesis of HNSCC. However in some carcinomas it occurs as an early event even in low grade neoplasias.