Assessing the Phenotype of a Homologous Recombination Deficiency Using High Resolution Array-Based Comparative Genome Hybridization in Ovarian Cancer
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Published:2023-12-14
Issue:24
Volume:24
Page:17467
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Magadeeva Svetlana1, Qian Xueqian1, Korff Nadine1, Flörkemeier Inken1ORCID, Hedemann Nina1, Rogmans Christoph1, Forster Michael2ORCID, Arnold Norbert12ORCID, Maass Nicolai1, Bauerschlag Dirk O.1ORCID, Weimer Jörg P.1ORCID
Affiliation:
1. Department of Gynaecology and Obstetrics, Christian-Albrechts-University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany 2. Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany
Abstract
Ovarian cancer (OC) cells with homologous recombination deficiency (HRD) accumulate genomic scars (LST, TAI, and LOH) over a value of 42 in sum. PARP inhibitors can treat OC with HRD. The detection of HRD can be done directly by imaging these genomic scars, or indirectly by detecting mutations in the genes involved in HR. We show that HRD detection is also possible using high-resolution aCGH. A total of 30 OCs were analyzed retrospectively with high-resolution arrays as a test set and 19 OCs prospectively as a validation set. Mutation analysis was performed by HBOC TruRisk V2 panel to detect HR-relevant mutations. CNVs were clustered with respect to the involved HR genes versus the OC cases. In prospective validation, the HRD status determined by aCGH was compared with external HRD assessments. Two BRCA mutation carriers did not have HRD. OC could approximately differentiate into two groups with characteristic CNV patterns with different survival rates. Mutation frequencies have a linear regression on the HRD score. Mutations in individual HR-relevant genes do not always indicate HRD. This may depend on the mutation frequency in tumor cells. The aCGH shows the genomic scars of an HRD inexpensively and directly.
Funder
German Federal Ministry of Education and Research Medical Health Science and Technology Project of Zhejiang Provincial Health Commission National Key R&D Program of China
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference46 articles.
1. Chang, L.C., Huang, C.F., Lai, M.S., Shen, L.J., Wu, F.L., and Cheng, W.F. (2018). Prognostic factors in epithelial ovarian cancer: A population-based study. PLoS ONE, 13. 2. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing;Lee;Nat. Genet.,2020 3. Shorokhova, M., Nikolsky, N., and Grinchuk, T. (2021). Chromothripsis-Explosion in Genetic Science. Cells, 10. 4. DNA repair mechanisms in cancer development and therapy;Torgovnick;Front. Genet.,2015 5. Base excision repair and its implications to cancer therapy;Grundy;Essays Biochem.,2020
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