ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Genetics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1593881
Combination of BRCA deep targeted sequencing and shallow whole genome sequencing to detect homologous recombination deficiency in ovarian cancer
Provisionally accepted
Thien-Phuc Nguyen Hoang1,2
Nam HB Tran1,2
Tien Anh Nguyen1,2My TT Ngo1,2Anh Duong Doan1,2Du Quyen Nguyen1,2Hung Sang Tang1,2Duy Sinh Nguyen1,2Cam Tu Nguyen Thi1,2Thanh Thuy Do Thi1Hoai-Nghia Nguyen1,2
Hoa Giang1,2
Lan N Tu1,2*- 1Medical Genetics Institute (Vietnam), Ho Chi Minh, Vietnam
- 2Gene Solutions, Ho Chi Minh City, Vietnam
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Backgrounds: Assessing homologous recombination deficiency (HRD) has been recommended by clinical guidelines for patients with ovarian cancer (OC) as it predicts sensitivity to poly (ADPribose) polymerase inhibitors (PARPi). However, HRD testing is complex and either inaccessible or unaffordable for majority of OC patients in developing countries. Consequently, the prevalence of HRD in OC remains unknown.We examined HRD status of 77 Vietnamese patients with OC using a new laboratorydeveloped test (HRD Insight, Gene Solutions). Tumor DNA was extracted from FFPE samples, followed by next-generation sequencing to detect deleterious or suspected deleterious variants in BRCA1/2 genes. Shallow whole genome sequencing was performed to determine the whole Genomic Instability (wGI) score by assessing the presence of large-scale intra-chromosomal copy number alterations.The assay was first benchmarked against commercial HRD kits including TruSight Oncology 500 HRD (Illumina), SOPHiA DDM HRD Solutions (Sophia Genetics) and HRD Focus Panel (AmoyDx), and showed an overall percent agreement of 90.0%, 96.3%, and 96.4% respectively. The successful rate of sequencing was 94.8% (73/77) and the prevalence of HRD in OC patients was 54.8% (40/73). BRCA mutations and positive wGI scores were found in 16.4% (12/73) and 47.9% (35/73) of the patients respectively. Among those with wild-type BRCA1/2, 40.5% of them had positive wGI scores and hence positive HRD. Age at diagnosis was not affected by both BRCA and wGI status.Conclusions: HRD Insight assay could accurately and robustly determine the HRD status of ovarian tissue samples, including those with low quality.
Keywords: Homologous recombination deficiency, ovarian cancer, PARPi, BRCA1/2, Genomic Instability
Received: 14 Mar 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Nguyen Hoang, Tran, Nguyen, Ngo, Doan, Nguyen, Tang, Nguyen, Nguyen Thi, Do Thi, Nguyen, Giang and Tu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lan N Tu, Medical Genetics Institute (Vietnam), Ho Chi Minh, Vietnam
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.