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• W1998058908 abstract "Detecting mutation in BRCA1/2 is a generally accepted strategy for screening ovarian cancers that have impaired homologous recombination (HR) ability and improved sensitivity to PARP inhibitor. However, a substantial subset of BRCA-mutant ovarian cancer patients shows less impaired or unimpaired HR ability, resulting in nonequivalent outcome after ovarian cancer development. We hypothesize that genomic instability provides a lifetime record of DNA repair deficiency and predicts ovarian cancer outcome. Based on the multi-dimensional TCGA ovarian cancer data, we developed a biological rationale-driven genomic instability score integrating somatic mutation and copy number change in a tumor genome. The score successfully divided BRCA-mutant ovarian tumors into cases of significantly improved outcome and cases of unimproved outcome. The score was also capable of discriminating HR-deficiency indicated by BRCA1 epigenetically silencing, EMSY amplification and homozygous deletion of core HR genes. We further found that the score was positively correlated with the complete response rate of chemotherapy and the rate of platinum-sensitivity, and predicted improved outcome of ovarian cancer, regardless of BRCA-mutation status. The score may have important value in outcome prediction and clinical trial design." @default.
• W1998058908 created "2016-06-24" @default.
• W1998058908 creator A5003905836 @default.
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• W1998058908 date "2014-12-01" @default.
• W1998058908 modified "2023-09-23" @default.
• W1998058908 title "A Genomic Instability Score in Discriminating Nonequivalent Outcomes of BRCA1/2 Mutations and in Predicting Outcomes of Ovarian Cancer Treated with Platinum-Based Chemotherapy" @default.
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• W1998058908 doi "https://doi.org/10.1371/journal.pone.0113169" @default.
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• W1998058908 hasPublicationYear "2014" @default.
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