Detecting TP53 mutations in paired liquid and tissue biopsies from patients with high-grade serous ovarian carcinomaShow others and affiliations
2025 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215Article in journal (Refereed) Epub ahead of print
Abstract [en]
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.
Place, publisher, year, edition, pages
John Wiley & Sons, 2025.
Keywords [en]
ctDNA, liquid biopsy, next generation sequencing, ovarian cancer biomarkers, UMI
National Category
Cancer and Oncology Gynaecology, Obstetrics and Reproductive Medicine Medical Genetics and Genomics
Research subject
Bioinformatics
Identifiers
URN: urn:nbn:se:his:diva-26082DOI: 10.1002/ijc.70277ISI: 001632794200001PubMedID: 41363274Scopus ID: 2-s2.0-105024319427OAI: oai:DiVA.org:his-26082DiVA, id: diva2:2022995
Funder
Sjöberg Foundation, 2021-01145Swedish Cancer Society, 21-1848Stiftelsen Assar Gabrielssons fond, FB22-67Stiftelsen Assar Gabrielssons fond, FB23-118Stiftelsen Assar Gabrielssons fond, FB22-79Stiftelsen Assar Gabrielssons fond, FB23-66Region Västra GötalandSwedish Cancer Society, 22-2080Swedish Research Council, 2021-01008Vinnova, 2020-04141Sjöberg Foundation
Note
CC BY 4.0
© 2025 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
First published: 09 December 2025
Correspondence Address: A. Linder; Sahlgrenska Center for Cancer Research, Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SE-405 30, Sweden; email: anna.linder@gu.se; K. Sundfeldt; Sahlgrenska Center for Cancer Research, Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; email: karin.sundfeldt@obgyn.gu.se; CODEN: IJCNA
The present study has been funded by the Sjöberg Foundation (2021-01145 to Karin Sundfeldt), Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (965552 to Karin Sundfeldt), Cancera and the Swedish Cancer Society (21-1848 to Karin Sundfeldt), the Assar Gabrielsson's Foundation (FB22-67, and FB23-118 to Anna Linder; FB22-79, and FB23-66 to Amanda Olsson Widjaja), the Lions Cancerfond Väst (2022 to Anna Linder), Nilsson-Ehle Endowments (2022 to Anna Linder), Gunvor och Ivan Svenssons stiftelsen till minne av deras son Ivan (2023, and 2024 to Anna Linder), and Kungl. Vetenskaps- och Vitterhets-Samhället (KVVS) (2020 to Anna Linder). Anders Ståhlberg is funded by Region Västra Götaland; Swedish Cancer Society [22-2080]; Swedish Research Council [2021-01008]; the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement [965065]; Sweden's Innovation Agency [2020-04141], and the Sjöberg Foundation.
2025-12-182025-12-182025-12-19Bibliographically approved