# Concordance of Genomic Alterations in Ovarian Cancer Tissues and Circulating-Tumor DNA: A Pilot Study

## TL;DR

This pilot study compares genomic alterations in ovarian cancer tissues and circulating tumor DNA, finding high gene-level agreement but differences in mutation detection.

## Contribution

The study introduces a novel approach using UMI technology to assess concordance between ctDNA and tissue in ovarian cancer with high sensitivity.

## Key findings

- cfDNA showed a 95.3% gene-level concordance with tissue, mainly due to agreement in wild-type genes.
- Liquid biopsy detected a broader mutational spectrum compared to tissue biopsies.
- Plasma-unique mutations had significantly lower variant allele frequencies than concordant mutations.

## Abstract

High-grade serous ovarian carcinoma (HGSOC) is characterized by profound genomic instability and spatial heterogeneity. Liquid biopsy, utilizing circulating tumor DNA (ctDNA), offers a non-invasive approach to capture the comprehensive mutational landscape of the disease. This pilot study evaluated the concordance of genomic alterations between cell-free DNA (cfDNA) and matched tumor tissue in patients with HGSOC. Twelve patients with HGSOC undergoing primary cytoreductive surgery were enrolled. Using the Macrogen® Axen™ Cancer Panel 2 with unique molecular identifier (UMI) technology for error suppression, we achieved a theoretical limit of detection of ~0.36% VAF. The mean cfDNA concentration was 107.3 ng/mL, showing a significant positive correlation with FIGO stage (p = 0.016). While the sensitivity of cfDNA to detect tissue-confirmed mutations was 57.6%, the overall gene-level concordance was 95.3%, largely driven by negative agreement in wild-type genes. Liquid biopsy revealed a significantly broader mutational spectrum (mean 9.67 alterations/patient) compared to tissue (5.50/patient). Crucially, concordant mutations exhibited high variant allele frequencies (VAFs) (mean 41.4%), whereas plasma-unique discordant mutations showed significantly lower VAFs (mean 7.31%, p < 0.001). These preliminary findings suggest that while tissue biopsy likely reflects the dominant clonal population, liquid biopsy may serve as a potential molecular mirror, capturing subclonal variants from spatially distinct metastatic sites and hypoxic niches.