Alterations of DNA Repair and Apoptosis Signaling Pathways in Taiwanese Oral Cavity Squamous Cell Carcinomas

Oral squamous cell carcinoma (OSCC) is the most rapidly raising male cancer in Taiwan. In 2010, OSCCs was the fourth most common cancer in males. In spite of improvements in surgical and radiotherapy treatment, the survival rates of OSCC have improved little over the past forty years. The most important determinant of a poor outcome within the first 2 years after treatment of the primary tumor is a high recurrence rate for primary tumors or the presence of a second primary tumor; these are often difficult cases involving radical surgical resectioning and resistance to radiotherapy or chemo-radiotherapy. Prediction of tumor behavior, such as metastatic potential and response to different treatments, would enable a more individualized approach by selecting the optimal treatment. To date, the most important factors predicting outcome of OSCC are tumor volume, grade and TNM stage. However, neither biologic behavior nor response to therapy can be fully explained by these factors. Thus, a deeper understanding of OSCC pathogenesis is needed to promote the development of improved therapeutic approaches. The genome-wide high-throughput analysis systems such as microsatellite markers, SNP array have now permitted rapid analyses of a large numbers of genes for somatic alterations. We have used Applied Biosystems PRISM Linkage Mapping Set-MD10 400 polymorphic microsatellite markers on 63 OSCCs and 32 minimally-deleted regions (MDRs) were determined. In addition, regions of copy number alterations were preliminarily identified by either Affymetrix 500K or Affymetrix SNP6.0 on 72 OSCCs (please see C012-1). Based on our previous studies and latest genome-wide analyses, we speculated that the major pathogenic pathways of Taiwanese OSCCs are DNA repair, membrane receptor and apoptosis signaling. Detailed analyses on membrane receptor signaling pathway now are undergoing (NSC99-2314-B-182A-036-MY3, I am as one of the co-investigators). Therefore, this three year project will focus on analysis of genes involved in DNA repair and apoptosis signaling pathways in 310 male OSCCs. The specific aims of this 3-year project are: 1) gene copy analysis of 11 genes involved in DNA repair and apoptosis signaling pathways, 2) loss of heterozygosity (LOH) analysis of 7 genes involved in DNA repair signaling pathway, 3) immunohistochemical analysis of protein expression for those genes as stated above, and 4) mutation analysis of p53 gene for those OSCCs without p53 mutation information (n = 105). We expect that the results obtained from this project will provide important information for the clinical management of OSCC in Taiwan.

Project ID:PC10301-1145
External Project ID:NSC101-2314-B182-048-MY3