Tumor suppressor gene detection in oral tumors for new therapeutic strategy

Naoki Katase, Mathieu Lefeuvre, Mehmet Gunduz, Hidetsugu Tsujigiwa, Silvia Susana Borkosky, Gul San Ara Sathi, Ryo Tamamura, Masae Fujii, Kenji Shimizu, Hitoshi Nagatsuka

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

In head and neck, oral and maxillofacial region, there are many kinds of neoplasms, which may originate from squamous epithelium, salivary glands and tooth germ etc. Generally, neoplasm development is considered to arise due to the cumulative abnorm alities of tumor-associated genes, i.e. oncogenes and tumor suppressor genes (TSGs). As for the neoplasms in head and neck, oral and maxillofacial regions, the responsible genes specifically associated with tumorigenesis and/or invasiveness have not been well understood. Therefore the biological characteristics of these neoplasms are yet to be determined. In order to establish a new approach for the better understanding, early diagnosis and advanced therapeutic strategies, we considered application of loss of heterozygosity (LOH) analysis for detection of TSGs.LOH analysis is a highly sensitive and specific method to detect allelic deletion of specific chromosomal locations. Briefly, paired samples of genomic DNA extracted from normal and tumor tissues of the same patients are used for the study. Certain sequences on the chromosomal loci are amplified by PCR using microsatellite markers. The PCR products are loaded into polyacrylamide gel electrophoresis and visualized with various methods including silver staining and SYBR green. Then the bands from normal and tumor DNA PCR products are compared. If the band form tumor DNA are weakened or disappeared as compared to normal counterpart after normalization with a band of housekeeping gene for each of normal and tumor DNA, LOH (+) is scored. Loci with frequent LOH might harbor TSGs.Based on the idea, we have reported several candidate TSGs as a carcinogenic as well as therapeutic target, including inhibition of growth (ING) and Dickkopf (Dkk) family of genes. LOH could be observed not only in malignant tumors but also in benign tumors. In this chapter, we will show the general data of LOH analysis in head and neck squamous cell carcinoma (HNSCC) and ameloblastoma as the actual examples.HNSCC is the 6th or 7th most occurring cancer worldwide. Despite improvement in surgery, radiation and chemotherapy, often HNSCC is difficult to be controlled in the cases with lymph nodal and/or distant metastasis. Therefore, its total survival rate is yet to be improved during decades. On the other hand, ameloblastoma is the most common odontogenic tumor, which possesses strong local invasiveness, although it is a benign tumor. Ameloblastoma generally occurs in the young population, and sometimes aggressive bone resection is needed, which might result in the impaired quality of life. Therefore, establishment of new and less aggressive therapeutic approaches are needed. Application of LOH analysis and combination with statistical analysis might be a powerful tool for detection of the role of candidate TSGs as prognostic factor.

Original languageEnglish
Title of host publicationOral Cancer
Subtitle of host publicationCauses, Diagnosis and Treatment
PublisherNova Science Publishers, Inc.
Pages169-188
Number of pages20
ISBN (Print)9781612093055
Publication statusPublished - Apr 1 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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  • Cite this

    Katase, N., Lefeuvre, M., Gunduz, M., Tsujigiwa, H., Borkosky, S. S., Sathi, G. S. A., Tamamura, R., Fujii, M., Shimizu, K., & Nagatsuka, H. (2011). Tumor suppressor gene detection in oral tumors for new therapeutic strategy. In Oral Cancer: Causes, Diagnosis and Treatment (pp. 169-188). Nova Science Publishers, Inc..