Genomic Scar Signatures Associated with Homologous Recombination Deficiency Predict Adverse Clinical Outcomes in Patients with Ovarian clear Cell Carcinoma
Abstract
We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC specimens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified as the strongest prognostic indicator in this patient group.Key messages Genomic scar signatures associated with HRD are less frequent in OCCC than in HGSC. Genomic scar signatures associated with HRD have an adverse prognostic impact in patients with OCCC. LOH score is the strongest adverse prognostic factor in patients with OCCC.
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Defects in homologous recombination repair can lead to genomic scars caused by the cancer cell's inability to accurately repair sites of double strand breaks.
“Defects in HRR can lead to the presence of “genomic scars” caused by the cancer cell’s inability to accurately repair sites of double strand breaks (DSBs).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Chao et al., 2018
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- Authors
- Chao, A., Lai, C.-H., Wang, T.-H., Jung, S.-M., Lee, Y.-S., Chang, W.-Y., Yang, L.-Y., Ku, F.-C., Huang, H.-J., Chao, A.-S., Wang, C.-J., Chang, T.-C., & Wu, R.-C.
- Affiliations
- Chang Gung University (TW)
- Ming Chuan University (TW)
- Chang Gung Memorial Hospital (TW)
- Corresponding author
- Wu, Ren-Chin
- ORCID
- Venue
- Journal of Molecular Medicine
- Published
- 2018-05-03
- Volume
- 96
- Issue
- 6
- Pages
- 527-536
- ISSN
- 0946-2716 (ISSN-L)
- 1432-1440
- OpenAlex
- W2801476439
- Cited by
- 20
- References
- 24
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 2 · 2017: 1
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chang Gung Medical Foundation (CMRPG3C0931/2/3 and CMRPG3H0351, CMRPG3E2021/2/3)
- Ministry of Science and Technology, Taiwan (106-2314-B-182-053-MY2, 106-2320-B-182-037-MY2)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- ovarian clear cell carcinoma, homologous recombination deficiency, loss of heterozygosity, telomeric allelic imbalance, copy number alterations, prognostic factors, high-grade serous carcinoma, progression-free survival, cancer-specific survival
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Middle Aged, Ovarian Neoplasms, Prognosis, Proportional Hazards Models, Adenocarcinoma, Clear Cell, Loss of Heterozygosity, Genomics, Young Adult, Homologous Recombination
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