Liquid biopsy as a tool in detection of circulating tumor DNA in High Grade Serous Carcinomas

Background: Ovarian cancer is the most deadly gynecologic cancer and high grade serous carcinomas(HGSC) accounts for the majority of these deaths. CA-125 remains the best characterized biomarker in ovarian cancer but unfortunately it is neither sensitive nor specific enough to be used for screening of the general population. Furthermore, there is no evidence that intensive monitoring of CA-125 during follow-up, improves overall survival rate or quality of life.
All cancers harbor genetic alterations in their DNA . These mutations occur at a negligible frequency in normal cells. The tumors shed DNA in big amounts into the blood stream and these molecules can be detected as circulating tumor DNA(ctDNA), called "liquid biopsies". Earlier studies of liquid biopsy, have shown a correlation between mutations found in ctDNA and different types of solid cancers. With this study we want to assess the detection of individually specific breakpoints in ctDNA in patients suffering from HGSC. With a high and precise detection rate this could be a sensitive and specific biomarker useful in follow-up, tailored treatment and possibly early detection.
Materials and methods: 20 patients with HGSC will be identified at Odense University Hospital and from each patient a tumor sample and a blood sample are collected.
The first method tested could be useful in tailored treatment and follow-up of patients. Here each tumor sample will undergo next generation sequencing of the entire genome to identify breakpoints specific for each ovarian tumor. Then 2-4 breakpoints will be chosen and it will be assessed if these can be found in plasma from the same patient.
The second method testes could potentially be useful in early detection. The plasma will be analyzed for known mutations found in HGSC and furthermore, chromosomal copy number aberrations will be identified.
Results: Results are expected in January 2017. The hypothesis is that we will find that ctDNA is well correlated to tumor DNA in patients with high grade serous carcinoma and that genetic mutations and copy number aberrations is detectable in circulating tumor DNA in plasma.
Perspectives: If the hypothesis is confirmed this study will create the basis for a future project assessing whether a change in ctDNA is seen earlier than a change in CA-125 and if so whether new and/or earlier treatment can change overall survival.