ArticlePloS one2014
A genomic instability score in discriminating nonequivalent outcomes of BRCA1/2 mutations and in predicting outcomes of ovarian cancer treated with platinum-based chemotherapy.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Prognostic significance of BRCA mutations in ovarian cancer: an updated systematic review with meta-analysis.Oncotarget · 2017Pooled it
- Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced gastric cancer.Journal for immunotherapy of cancer · 2022Trial
- Predictive biomarkers for the efficacy of PARP inhibitors in ovarian cancer: an updated systematic review.BJC reports · 2025Article
- expHRD: an individualized, transcriptome-based prediction model for homologous recombination deficiency assessment in cancer.BMC bioinformatics · 2024Article
- CA-125 KELIM as an Alternative Predictive Tool to Identify Which Patients Can Benefit from PARPi in High-Grade Serous Advanced Ovarian Cancer: A Retrospective Pilot Diagnostic Accuracy Study.International journal of molecular sciences · 2024Article
- Review
- Clinico-genomic Characterization of ATM and HRD in Pancreas Cancer: Application for Practice.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Computational detection of a genome instability-derived lncRNA signature for predicting the clinical outcome of lung adenocarcinoma.Cancer medicine · 2022Article
- A novel genomic instability-derived lncRNA signature to predict prognosis and immune characteristics of pancreatic ductal adenocarcinoma.Frontiers in immunology · 2022Article
- Identification of genomic instability related lncRNA signature with prognostic value and its role in cancer immunotherapy in pancreatic cancer.Frontiers in genetics · 2022Article
- Medium levels of transcription and replication related chromosomal instability are associated with poor clinical outcome.Scientific reports · 2021Article
- Development and Validation of a Mutational Burden-Associated LncRNA Signature for Improving the Clinical Outcome of Hepatocellular Carcinoma.Life (Basel, Switzerland) · 2021Article
- Tumor genomic, transcriptomic, and immune profiling characterizes differential response to first-line platinum chemotherapy in high grade serous ovarian cancer.Cancer medicine · 2021Article
- Combination Treatment with an Antibody-Drug Conjugate (A1mcMMAF) Targeting the Oncofetal Glycoprotein 5T4 and Carboplatin Improves Survival in a Xenograft Model of Ovarian Cancer.Targeted oncology · 2019Article
- PARP Inhibitors in Ovarian Cancer: The Route to "Ithaca".Diagnostics (Basel, Switzerland) · 2019Review
- Genomic evolution of cancer models: perils and opportunities.Nature reviews. Cancer · 2019Review
- Article
- Clinical importance of the EMSY gene expression and polymorphisms in ovarian cancer.Oncotarget · 2018Article
- Promoter methylation of DNA damage repair (DDR) genes in human tumor entities:Clinical epigenetics · 2018Article
- The expression of miRNAs is associated with tumour genome instability and predicts the outcome of ovarian cancer patients treated with platinum agents.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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