TY - JOUR
T1 - Predictive utility of circulating methylated DNA in serum of melanoma patients receiving biochemotherapy
AU - Mori, Takuji
AU - O'Day, Steven J.
AU - Umetani, Naoyuki
AU - Martinez, Steve R.
AU - Kitago, Minoru
AU - Koyanagi, Kazuo
AU - Kuo, Christine
AU - Takeshima, Teh Ling
AU - Milford, Robert
AU - Wang, He Jing
AU - Vu, Vu D.
AU - Nguyen, Sandy L.
AU - Hoon, Dave S.B.
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2005.02.9876
DO - 10.1200/JCO.2005.02.9876
M3 - Article
C2 - 16361635
AN - SCOPUS:33644828776
SN - 0732-183X
VL - 23
SP - 9351
EP - 9358
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 36
ER -
