| Summary: | <p>Abstract</p> <p>Background</p> <p>We recently showed that LOH proximal to <it>M6P/IGF2R</it> locus (<it>D6S1581</it>) in primary ovarian tumors is predictive for the presence of disseminated tumor cells (DTC) in the bone marrow (BM). For therapy-monitoring, it would be highly desirable to establish a blood-based biomarker. Therefore, we quantified circulating DNA (cirDNA) in sera of 63 ovarian cancer patients before surgery and after chemotherapy, measured incidence of LOH at four cancer-relevant chromosomal loci, correlated LOH with tumor cell spread to the BM and evaluated prognostic significance of LOH.</p> <p>Methods</p> <p>cirDNA was fractionated into high- and low molecular-weight fraction (HMWF, LMWF) for LOH-profiling, utilizing PCR-based fluorescence microsatellite analysis. BM aspirates were analyzed for DTC by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3.</p> <p>Results</p> <p>cirDNA levels in the HMWF before surgery were predictive for residual tumor load (p = 0.017). After chemotherapy, we observed a significant decline of cirDNA in the LMWF (p = 0.0001) but not in the HMWF. LOH was prevalently detected in the LMWF with an overall frequency of 67%, only moderately ablating after chemotherapy (45%). Before surgery, LOH in the LMWF at marker <it>D10S1765</it> and <it>D13S218</it> significantly correlated with tumor grading and FIGO stage (p = 0.033, p = 0.004, respectively). In both combined fractions, LOH at <it>D6S1581</it> additionally associated with overall survival (OS) (p = 0.030). Moreover, solely LOH at <it>D10S1765</it> in LMWF after therapy correlated with DTC in BM after therapy (p = 0.017).</p> <p>Conclusion</p> <p>We demonstrate the applicability and necessity of DNA-fractionation prior to analyzing circulating LOH and identify LOH at <it>D10S1765</it> and <it>D6S1581</it> as novel blood-based biomarkers for ovarian cancer, being relevant for therapy-monitoring.</p>
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