Epithelial ovarian carcinoma (EOC) is highly fatal because of the risk of resistance to therapy and recurrence. We performed whole-exome sequencing of blood and tumor tissue pairs of 50 patients with surgically resected EOC. Compared with sensitive patients, platinum-resistant patients had a significantly higher somatic mutational rate in <i>TP53</i> and lower in several genes from the Hippo pathway. We confirmed the pivotal role of somatic mutations in homologous recombination repair genes in platinum sensitivity and favorable prognosis of EOC patients. Implementing the germline homologous recombination repair profile significantly improved the prediction. In addition, distinct mutational signatures, for example, SBS6, and overall mutational load, somatic mutations in <i>PABPC1</i>, <i>PABPC3</i>, and <i>TFAM</i> co-segregated with the resistance status, high-grade serous carcinoma subtype, or overall survival of patients. We generated germline and somatic genetic landscapes of prognostically different subgroups of EOC patients for further follow-up studies focused on utilizing the observed associations in precision oncology.

3rd Faculty of Medicine Charles University Prague Czech Republic

Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Gynecology and Obstetrics 3rd Faculty of Medicine Charles University and University Hospital Královské Vinohrady Prague Czech Republic

Department of Gynecology and Obstetrics Faculty of Medicine and University Hospital in Pilsen Charles University Pilsen Czech Republic

Department of Pathology and Molecular Medicine 2nd Faculty of Medicine and Motol University Hospital Charles University Prague Czech Republic

Toxicogenomics Unit National Institute of Public Health Prague Czech Republic

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$a Hlaváč, Viktor $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic $u Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic $1 https://orcid.org/0000000306950552

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$a Whole-exome sequencing of epithelial ovarian carcinomas differing in resistance to platinum therapy / $c V. Hlaváč, P. Holý, R. Václavíková, L. Rob, M. Hruda, M. Mrhalová, P. Černaj, J. Bouda, P. Souček

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$a Epithelial ovarian carcinoma (EOC) is highly fatal because of the risk of resistance to therapy and recurrence. We performed whole-exome sequencing of blood and tumor tissue pairs of 50 patients with surgically resected EOC. Compared with sensitive patients, platinum-resistant patients had a significantly higher somatic mutational rate in &lt;i&gt;TP53&lt;/i&gt; and lower in several genes from the Hippo pathway. We confirmed the pivotal role of somatic mutations in homologous recombination repair genes in platinum sensitivity and favorable prognosis of EOC patients. Implementing the germline homologous recombination repair profile significantly improved the prediction. In addition, distinct mutational signatures, for example, SBS6, and overall mutational load, somatic mutations in &lt;i&gt;PABPC1&lt;/i&gt;, &lt;i&gt;PABPC3&lt;/i&gt;, and &lt;i&gt;TFAM&lt;/i&gt; co-segregated with the resistance status, high-grade serous carcinoma subtype, or overall survival of patients. We generated germline and somatic genetic landscapes of prognostically different subgroups of EOC patients for further follow-up studies focused on utilizing the observed associations in precision oncology.

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$a Holý, Petr $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic $u Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic $u Third Faculty of Medicine, Charles University, Prague, Czech Republic $1 https://orcid.org/0000000269505563

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$a Hruda, Martin $u Department of Gynecology and Obstetrics, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, Prague, Czech Republic

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$a Mrhalová, Marcela $u Department of Pathology and Molecular Medicine, Second Faculty of Medicine and Motol University Hospital, Charles University, Prague, Czech Republic

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$a Souček, Pavel $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic pavel.soucek@szu.cz $u Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic $1 https://orcid.org/0000000242946799

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