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Whole-exome sequencing of epithelial ovarian carcinomas differing in resistance to platinum therapy.


ABSTRACT: 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.

SUBMITTER: Hlavac V 

PROVIDER: S-EPMC9574568 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Whole-exome sequencing of epithelial ovarian carcinomas differing in resistance to platinum therapy.

Hlaváč Viktor V   Holý Petr P   Václavíková Radka R   Rob Lukáš L   Hruda Martin M   Mrhalová Marcela M   Černaj Petr P   Bouda Jiří J   Souček Pavel P  

Life science alliance 20221013 12


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 repai  ...[more]

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