Abstract IA17: Physical and in silico methods for improving sensitivity of detection of ctDNA for personalized medicine in high-grade serous ovarian cancer
- Abstract:
- Abstract Early detection of high-grade serous ovarian cancer (HGSOC) remains a major challenge owing to early metastasis from the fallopian tube and lack of specific symptoms or clinical signs. Noninvasive analysis of circulating tumor DNA (ctDNA) for common mutations has the potential to provide highly specific tests for detecting ovarian cancer. We have previously shown that TP53 ctDNA is highly correlated with total volume of disease using 3D volumetric reconstruction of CT images. However, detection of ctDNA requires ctDNA concentration to be greater than 0.5% for adequate sensitivity. Improved methods for detection of ctDNA are also required for reliable response monitoring during treatment and detection of minimal residual disease after surgery and systemic therapy. I will discuss recent approaches in our lab that have investigated whether size selection of DNA fragments from plasma can increase the detection of ctDNA by enrichment away from cell free DNA of non-tumor origin. The majority of HGSOC ctDNA is in a size range of 90-150 bp based on whole-genome sequencing of cell free DNA from women with relapsed HGSOC and from HGSOC mouse xenografts. Using physical size selection in 35 patients with recurrent HGSOC and 16 additional patients with other cancer types yielded enrichment of mutated DNA fractions by a median of 4.3-fold allowing improved analysis by targeted, whole-exome, and whole-genome sequencing. This allowed identification of new mutations that otherwise were not observed. Size selection allows detection of tumor alterations masked by non-tumor DNA in plasma, and could improve the sensitivity of liquid biopsy for applications in early diagnosis, detection of minimal residual disease and for establishing mutational signatures from ctDNA. Citation Format: James D. Brenton. Physical and in silico methods for improving sensitivity of detection of ctDNA for personalized medicine in high-grade serous ovarian cancer. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA17.
- Authors:
- JD Brenton
- Journal:
- Clinical Cancer Research
- Citation info:
- 24(15_Supplement):IA17-IA17
- Publication date:
- 1st Aug 2018
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- DOI