Correlation between thymidylate synthase (TS) genotype, clinical outcome, and TS mRNA expression in subjects treated with oxaliplatin (OX) and capecitabine (Cape)

13073 Background: TS mRNA has a unique tandemly repeated 28-base pair sequence in the 5’ UTR & is polymorphic in the number of this repeat (2 or 3). Homozygosity for the 3-repeat sequence has been associated with increased TS protein content in tumor samples, & decreased likelihood of clinical benefit with TS-directed therapy. This study assessed the possible association of TS genotype with clinical outcome in subjects receiving OX &Cape in an IRB-approved Phase I clinical trial. Methods: Pre-therapy genomic DNA was isolated from peripheral blood mononuclear cells in 88 subjects treated with OX 130 mg/m2 day 1 & Cape 600–1500 mg/m2 twice daily days 1–5 & 8–12 every 3-weeks. The number of tandem repeats was determined by the size of the PCR-amplified DNA fragments by staining after 3% agarose gel electrophoresis. The genotype was also compared to TS mRNA expression that was previously determined by quantiitative real-time PCR in microdissected specimens of metastatic tumor tissue. Results: The majority of ...