Fractional allelic loss as a potential biomarker of risk prediction in early-stage mucinous ovarian tumors of low malignant potential

Ovarian tumors of low malignant potential (LMP) appear to be intermediate between adenomas and ovarian carcinomas. Such tumors are often associated with a significantly better prognosis than for ovarian carcinomas. However, a subset of LMPs can progress and become lethal even in patients with early-stage disease. In order to seek sensitive diagnostic tools to monitor patients after surgical therapy, we performed a genome-wide scan for LOH in 37 early-stage mucinous LMPs using 91 polymorphic microsatellite markers at an average interval of 50 cM across all of the human chromosomes and 25 LOH markers reported to be associated with ovarian carcinoma. Fractional allelic loss (FAL) values were calculated as (loci scored with LOH)/(total informative loci) for each sample. With respect to tumor recurrence, high FAL values were more frequent in recurrent tumors than in nonrecurrent tumors. Using the screening markers, FAL values for recurrent tumors were significantly higher than for non-recurrent tumors (19.8% vs 6.3%, respectively, p < 0.0001). Similar results were obtained using the hotspot markers (22.2% vs 7.1%. respectively, p < 0.0001). A significant correlation between FAL values obtained using screening markers and those based on hotspot markers was observed (R = 0.460, p = 0.003). Our findings suggest that a specific type of genetic instability (i.e., chromosomal instability, CIN) may exist in mucinous LMPs. and that this instability may indicate tumors with an aggressive biological nature. Therefore, FAL values may represent a new biomarker for risk prediction in early-stage mucinous LMP tumors.

Ovarian Carcinoma; Mucinous LMP; Loss of heterozygosity (LOH); Fractional allelic loss.

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