Abstract 2839: Specific mutant tumor DNA can be detected in ovarian cystic fluid of an unknown ovarian tumor cyst

Abstract

Abstract Can we detect rare mutations in ovarian cystic fluid of unknown severity in order to develop a molecular genetic test for epithelial ovarian cancer? Background: Benign and malignant ovarian cysts are difficult to distinguish. Early diagnose is life saving, however 75% of ovarian adenocarcinomas is found in late stage. Approx. one operated ovarian cyst in 7-10 are found to be cancer and potentially life-threatening, subjecting the woman to unnecessary oophorectomy and morbidity. A genetic test of fine needle aspirated cystic fluid has to be very accurate to be able to substitute the histopathologic examination following surgery. Methods: DNA was purified from 78 ovarian cystic fluids (collected at the time of operation) from serous adenomas/adenocarcinomas and corresponding tumor tissues and subjected to state-of-the-art genetic analysis. We evaluated ∼10,000 bp for subtle mutations (single base substitutions, small insertions, small deletions). Under the conditions used, mutations present in >0.1% of template molecules could be detected. The analyses were carried out in a completely blind fashion. We then evaluated the DNA of the primary tumor. Results: We detected zero, one, or two mutations per cyst. The same mutations were identified in the corresponding tumor tissue, and no others. This dramatically confirms the specificity of the approach. 91% of the malignant cysts (n = 32) had at least one mutation and 62% of these were in TP53; 17% in low (n = 12) and 90% in high (n = 20) grade serous adenocarcinoma regardless of stage. In low-grade tumors mutations in KRAS dominated over PIK3C and PTEN. 65% of the borderline type (LMP n = 20) tumors had a BRAF V600E mutation. The mutant allelic fraction was much higher in malignant than benign tumors; the DNA concentration was relatively low in 20 benign cysts and no mutations were identified in this group consisting of 10 serous adenoma and 10 simple cysts (healthy controls). Results will be correlated to survival. Conclusion: Data proofs that we can detect mutant tumor DNA corresponding to the primary ovarian tumor in the ovarian cystic fluid. Data suggest that gene-testing of ovarian cystic fluid could aid in diagnostics and further guide its management. Citation Format: Karin Sundfeldt, Björg Kristjansdottir, Bert Vogelstein. Specific mutant tumor DNA can be detected in ovarian cystic fluid of an unknown ovarian tumor cyst. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2839. doi:10.1158/1538-7445.AM2015-2839