# Detecting TP53 mutations in paired liquid and tissue biopsies from patients with high‐grade serous ovarian carcinoma

## TL;DR

This study introduces a new TP53 mutation panel for detecting high-grade serous ovarian carcinoma using both liquid and tissue biopsies, showing promising results for non-invasive diagnosis.

## Contribution

A novel TP53 mutation panel using unique molecular identifier-based sequencing for sensitive detection of HGSC in multiple sample types.

## Key findings

- Pathogenic TP53 mutations were identified in all patients across multiple sample types.
- The TP53 mutation panel successfully detected mutations with as little as 2.6 ng of DNA.
- Consistent mutations were found in ascites, ovarian cyst fluid, and plasma samples.

## Abstract

High‐grade serous ovarian carcinoma (HGSC) is the most lethal form of ovarian carcinoma, often diagnosed at advanced stages due to non‐specific symptoms and the lack of reliable screening methods. This proof‐of‐concept study aimed to develop a robust TP53 mutation panel for detecting HGSC through targeted DNA sequencing in both liquid and solid biopsies. We constructed a custom TP53 gene panel and utilized a PCR‐based unique molecular identifier approach for next‐generation sequencing to analyze 94 samples from 11 patients diagnosed with HGSC, including primary tumor, plasma, ascites, ovarian cyst fluid, vaginal, endocervical and endometrial samples. Detected TP53 mutations were analyzed, categorized, and their frequencies calculated. Pathogenic TP53 mutations were identified in all patients, with 91% of the patients exhibiting one unique paired mutation across three or more sample types. The panel demonstrated high sensitivity and technical reproducibility, successfully detecting TP53 mutations across all sample types, with as little as 2.6 ng of DNA. TP53 mutations were consistently found in ascites, ovarian cyst fluid, and plasma samples, confirming the presence of pathogenic mutations in each sample type across all patients. This study underscores the potential of liquid biopsies in clinical molecular diagnostics. The TP53 mutation panel presented in this proof‐of‐concept study offers a promising approach for differential diagnostics and detection of HGSC, informative data prior to extended investigation and first‐line treatment guidance.

High‐grade serous ovarian carcinoma is often diagnosed at advanced stages due to non‐specific symptoms and the lack of reliable screening methods. This proof‐of‐concept study introduces a novel TP53 mutation panel using unique molecular identifier‐based next‐generation sequencing for sensitive detection of high‐grade serous ovarian carcinoma in liquid and solid biopsies. With minimal DNA input (as little as 2.6 ng), the same pathogenic mutation was identified in multiple sample types from each patient. The findings highlight the potential of non‐invasive liquid biopsies for high‐grade serous ovarian carcinoma detection, offering a promising tool in clinical molecular diagnostics and treatment decision‐making.