Predictive utility of circulating methylated DNA in serum of melanoma patients receiving biochemotherapy

Takuji Mori, Steven J. O'Day, Naoyuki Umetani, Steve R. Martinez, Minoru Kitago, Kazuo Koyanagi, Christine Kuo, Teh Ling Takeshima, Robert Milford, He Jing Wang, Vu D. Vu, Sandy L. Nguyen, Dave S B Hoon

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

Purpose: Currently, no validated blood-based assays accurately predict treatment response or outcome in melanoma patients. We hypothesized that methylation of tumor-related genes detected in serum DNA could predict disease outcome and therapeutic response in patients receiving concurrent biochemotherapy (BC) for metastatic melanoma. Patients and Methods: American Joint Committee on Cancer stage IV melanoma patients (N = 50) had blood drawn before administration of BC. Patients (n = 47) were classified as BC responders or nonresponders. Responders (n = 23) demonstrated a complete or partial response following BC; nonresponders (n = 24) demonstrated progressive disease. Hypermethylation of Ras association domain family 1 (RASSF1A), retinoic acid receptor-β2 (RAR-β2), and O6-methylguanine DNA methyltransferase (MGMT) genes were assessed by methylation-specific polymerase chain reaction. Results: Circulating methylated RASSF1A was significantly less frequent for responders (three of 23 patients; 13%) than nonresponders (10 of 24 patients; 42%; P = .028). Patients with RASSF1A, RAR-β2, or at least one serum methylated gene had significantly worse overall survival than patients with no methylated genes (log-rank, P = .013, .021, and .01, respectively). Methylated RASSF1A was the only factor that significantly correlated with overall survival and BC response (risk ratio, 2.38; 95% CI, 1.16 to 4.86; P = .018; odds ratio = 0.21; 95% CI, 0.05 to 0.90; P = .036). Conclusion: Detection of circulating methylated DNA in serum can predict response to BC and disease outcome.

Original languageEnglish (US)
Pages (from-to)9351-9358
Number of pages8
JournalJournal of Clinical Oncology
Volume23
Issue number36
DOIs
StatePublished - 2005

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Mori, T., O'Day, S. J., Umetani, N., Martinez, S. R., Kitago, M., Koyanagi, K., Kuo, C., Takeshima, T. L., Milford, R., Wang, H. J., Vu, V. D., Nguyen, S. L., & Hoon, D. S. B. (2005). Predictive utility of circulating methylated DNA in serum of melanoma patients receiving biochemotherapy. Journal of Clinical Oncology, 23(36), 9351-9358. https://doi.org/10.1200/JCO.2005.02.9876