A Sensitive and Transparent Method for Tumor-Informed Detection of Circulating Tumor DNA in Ovarian Cancer Using Whole-Genome Sequencing

Christine Fribert Thusgaard ^1,2, Sepideh Sadegh ^3,4, Kirsten Marie Jochumsen ^1,2

⁰Department of Gynecology and Obstetrics, Odense University Hospital, 5000 Odense, Denmark.

International Journal of Molecular Sciences +

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January 8, 2025

View abstract on PubMed

Summary

A new method enhances circulating tumor DNA (ctDNA) detection in ovarian cancer (OC) using whole-genome sequencing. This tumor-informed approach significantly improves ctDNA signal analysis for potential survival benefits.

Area Of Science

Oncology
Genomics
Biomarker Discovery

Background

Circulating tumor DNA (ctDNA) shows promise for improving ovarian cancer (OC) survival through treatment monitoring and early relapse detection.
Establishing an optimal ctDNA analysis method for OC is crucial for clinical application.

Purpose Of The Study

To develop and evaluate a tumor-informed whole-genome sequencing method for sensitive ctDNA detection in ovarian cancer patients.
To assess the efficacy of a novel plasma pool filtering approach in improving ctDNA signal-to-noise ratio and accuracy.

Main Methods

Whole-genome sequencing of tumor and plasma samples from 10 OC patients at diagnosis.
Application of basic filters (read depth, allelic depth, variant allele frequency) for ctDNA analysis.
Implementation of a new plasma pool filtering strategy to remove artefacts and enhance ctDNA signal.

Main Results

Basic filtering methods provided only minor improvements in signal-to-noise ratio (S2N).
The addition of the plasma pool filter significantly improved ctDNA signal detection, as evidenced by enhanced S2N and z-scores.
The developed tumor-informed method demonstrated considerable potential for ctDNA signal detection in OC.

Conclusions

A tumor-informed whole-genome sequencing approach combined with a plasma pool filter is a promising method for ctDNA detection in ovarian cancer.
This method offers significant potential for improving ctDNA signal analysis, despite the study's limited patient cohort.
Further validation is warranted to fully establish this method for clinical use in OC management.

Keywords:

carcinoma circulating tumor DNA epithelial ovarian carcinoma liquid biopsy single-nucleotide variant single-nucleotide variant detection whole-genome sequencing