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Prognostic Significance of Circulating Microsatellite Markers in the Plasma of Melanoma Patients

Department of Molecular Oncology [B. T., Y. F., D. S. B. H.] and Division of Biostatistics [H-J. W.], John Wayne Cancer Institute, Saint John’s Health Center, Santa Monica, California 90404 [L. J. F., D. L. M.]

Purpose: Multiple genetic alterations including loss of heterozygosity (LOH) occur commonly in melanoma tumors. We demonstrated previously free-circulating DNA microsatellites with LOH in the blood of melanoma patients. These LOH markers in plasma may be useful as surrogates for subclinical disease progression. The purpose of this study was to determine whether the presence of circulating tumor microsatellite markers in the preoperative blood from patients with melanoma has prognostic utility.

Experimental Design: Plasma was analyzed for the presence of LOH at six chromosome regions, which are common for allelic loss in melanoma tumors, in 57 patients undergoing surgical resection of all of the clinically apparent disease.

Results: LOH was detected in 32 of 57 patients (56%). Both LOH incidence and frequency correlated with advancing American Joint Committee on Cancer stage. In patients with American Joint Committee on Cancer stage III, the presence of LOH as an independent variable in preoperative plasma was significantly associated (P = 0.05) with an increased risk of death. Furthermore, LOH at microsatellite marker D1S228 in the plasma of patients with advanced disease correlated significantly (P = 0.0009) with a poorer survival after surgical resection. LOH commonly found in melanoma tumors can be successfully identified in the plasma of a patient, providing a potentially less invasive route for following genetic changes that serve as molecular surrogates for assessing subclinical disease progression.

Conclusions: This study provides evidence that blood testing for circulating tumor genetic markers may provide valuable prognostic information and guide future therapy.

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