Mitotic checkpoint gene CHFR methylation in pretreatment serum DNA of docetaxel (doc)/cisplatin (cis)-treated stage IV non-small cell lung cancer (NSCLC) patients (p)

Abstract

7056 Background: CHFR (checkpoint with forkhead-associated and ring finger) regulates a prophase delay in cells exposed to agents that disrupt microtubules. Epigenetic inactivation of CHFR is a frequent event in human tumors, leading to impaired checkpoint function and enhanced sensitivity to docetaxel. We hypothesized that serum DNA methylation of CHFR could be a predictor of longer survival in p treated with doc/cis. Methods: Sodium bisulfite modified serum DNAwas used as the template for methylation-specific PCR assay. DNA was obtained from 600 doc/cis-treated stage IV NSCLC p. Results: Preliminary data on 301 p is available. The frequency of CHFR hypermethylation was 32.6%. There was no association between methylation and performance status (PS), age, gender, histology, response, 14–3-3σ serum DNA methylation, polymorphisms in lymphocyte DNA (ERCC1 118 C/T, ERCC1 C8092A, XRCC3 241 ThrMet), or tumor ERCC1 mRNA levels. Overall, there was a tendency to better median survival (MS) for p with methylated CHFR. In p with PS 0, MS was 33 months (m) for 41 p with methylated CHFR and 12 m for 64 p with unmethylated CHFR (P = 0.23). In p >66 years (y), MS was not reached for 31 p with methylated CHFR and 9.6 m for 80 p with unmethylated CHFR (P = 0.01), while in p <66 y, MS was 9.4 m for 67 p with methylated CHFR and 10 m for 123 p with unmethylated CHFR (P = 0.62). p with both 14–3-3σ and CHFR methylation showed a tendency to longer survival. Final data on 600 p will be presented. Conclusions: Early findings indicate that CHFR methylation in elderly p predicts a significant survival benefit in doc/cis-treated NSCLC. No significant financial relationships to disclose.