gms | German Medical Science

77. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

24.05. - 28.05.2006, Mannheim

Methylation status of tumor-associated genes in squamous cell cancer of the head and neck

Meeting Abstract

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  • corresponding author Annett Sandner - Martin-Luther-University Halle-Wittenberg, Depatment of Otolaryngology, Head and Neck Surgery, Halle/ Saale, Germany
  • Katrin Baier - Martin-Luther-University Halle-Wittenberg, Department of human genetics and medical biology, Halle/ Saale, Germany
  • Marc Boris Bloching - Martin-Luther-University Halle-Wittenberg, Depatment of Otolaryngology, Head and Neck Surgery, Halle/ Saale, Germany
  • Reinhard Dammann - Martin-Luther-University Halle-Wittenberg, Department of human genetics and medical biology, Halle/ Saale, Germany

German Society of Otorhinolaryngology, Head and Neck Surgery. 77th Annual Meeting of the German Society of Otorhinolaryngology, Head and Neck Surgery. Mannheim, 24.-28.05.2006. Düsseldorf, Köln: German Medical Science; 2006. Doc06hno075

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hno2006/06hno075.shtml

Veröffentlicht: 7. September 2006

© 2006 Sandner et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: Aberrant promotor methylation is one of the major mechanisms in the transcriptional inactivation of certain tumor-associated genes. Concurrent methylation analysis of multiple, functionally distinct genes may provide important imformation on their differential alterations and potential association in carcinogenesis of head and neck tumors.

The purpose of this study was to examine the methylation profile of various squamous cell cancers of the head and neck and correlate the methylation status with clinicopathological features.

Material and Method: We analyzed aberrant DNA methylation at ten genes (RASSF1A, P16, MGMT, DAPK, RARß, Rb, MLH1, E-cad, GSTP1, RASSF4) in 31 primary tumors and corresponding normal mucosa. These genes were tested by methylation-specific PCR. We used different primer to identify methylated and unmethylated alleles and resolved it on 2% TBE gels together with a 100bp ladder. In vitro methylated HeLa DNA and human fibroblasts were used as control.

Results: 87% (27/31) of the primary tumors displayed promoter methylation in at least one gene, 45% (14/31) at three or more genes. Most frequent the RARß gene promoter was methylated (65,4%). At DAPK and MGMT promoter methylation was observed in 44,4%. Higher tumor stages tend to result in more frequently promotor methylation, but this was not statistically significant. Patients suffered from a recurrence in the study period had also more frequent promoter methylations. Interestingly aberrant promoter methylation of MGMT correlates with recurrent tumor in 75%.

Discussion: Our study demonstrates frequent methylation of CpG islands in tumor suppressor genes such as RARß, DAPK and MGMT. This is in accordance with other studies [1], [2]. Methylation of MGMT correlates with poor prognosis. The same has been proven for RASSF1A in lung carcinoma [3]. Others [4] found a positive correlation between inactivation of the p16 tumor suppressor gene through promoter methylation and lymph node metastasis. Aberrant methylation regard as useful molecular marker to predict the characteristics of disease and patients prognosis [5].

Conclusion: Our findings imply that concurrent methylation analysis provides important information on the relative functional status of these genes in HNSC tumorgenesis. The limited results suggest that epigenetic alterations may be a valuable prognostic indicator in HNSCC but further prospective trials are needed to further establish these observations.


References

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Ha PK, Califano JA. Promotor methylation and inactivation of tumor-sppressor genes in oral squamous-cell carcinoma. Lancet Oncol 2006; 7: 77-82
2.
Maruya S et al. Differential Methylation Status of Tumor-Associated Genes in Head and Neck Squamous Carcinoma: Incidence and Potential Implications. Clin Cancer Res 2004; 10: 3825-3830
3.
Dammann R et al. CpG island methylation and expression of tumor associated genes in lung carcinoma. Eur J Cancer 2005; 41: 1223-1236
4.
Ishida E et al. Promotor hypermethylation of p14ARS is a key alteration for progression of oral squamous cell carcinoma. Oral Oncology 2005; 41: 614-622
5.
Ogi K et al. Abberant Methylation of Multiple Genes and Clinicopathological Features in Oral Squamous Cell Carcinoma. Clin Cancer Res 2002; 8: 3164-3171