Abstract for presentation at 11th International Congress of Human Genetics

Inter-individual differences of treatment response to cancer therapy have become a challenging problem. The new field of pharmacogenomics, using DNA microarray analysis, focuses on the genetic determinants of drug response at many levels: DNA, RNA, protein and epigenetic factors. DNA modifications of mutations, amplifications, and deletions, RNA expression levels including micro RNA (miRNA) expression, changes in protein content, methylation status and combinations thereof can be explored globally to elucidate their component in diagnosis and treatment outcome.
For example oligodendrogliomas comprise more than 20% of all gliomas (the most common primary central nervous system tumors in adults). Compared with most other gliomas, oligodendrogliomas have a better prognosis and thus accurate diagnosis is essential. Although oligodendrogliomas are also more sensitive to chemotherapy, the response rate to chemotherapy is between 40–70%. To better understand this inter-individual variability response we used resected specimens of oligodendrogliomas before treatment with the oral alkylating agent temozolomide. Patients were followed with serial brain MRI scans every two months to record time to progression. Time to progression is defined as the time required for interval increase in tumor size by greater than 25%. We conducted global gene expression profiling, miRNA profiling and global comparative genomic analysis to determine the most predictive combination of data resulting in better diagnosis and personalized chemotherapy administration.