ArticlePloS one2013
Tumor mutation burden forecasts outcome in ovarian cancer with BRCA1 or BRCA2 mutations.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 146 citations in OpenAlex.
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- Mutation burden and other molecular markers of prognosis in colorectal cancer treated with curative intent: results from the QUASAR 2 clinical trial and an Australian community-based series.The lancet. Gastroenterology & hepatology · 2018Trial
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- The Search for Genomic Biomarkers of Response to Immunotherapy in Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Transcript-Targeted Therapy Based on RNA Interference and Antisense Oligonucleotides: Current Applications and Novel Molecular Targets.International journal of molecular sciences · 2022Review
- Utility of Homologous Recombination Deficiency Biomarkers Across Cancer Types.JCO precision oncology · 2022Article
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- Neoantigens and the tumor microenvironment play important roles in the prognosis of high-grade serous ovarian cancer.Journal of ovarian research · 2022Article
- Clinical Characteristics in the Prediction of Posttreatment Survival of Patients with Ovarian Cancer.Disease markers · 2022Article
- Prognostic value of tumor mutation burden and the relationship between tumor mutation burden and immune infiltration inGland surgery · 2022Article
- A prognostic signature based on adenosine metabolism related genes for ovarian cancer.Frontiers in oncology · 2022Article
- Utility of Homologous Recombination Deficiency Biomarkers Across Cancer Types.JCO precision oncology · 2021Article
- neoDL: a novel neoantigen intrinsic feature-based deep learning model identifies IDH wild-type glioblastomas with the longest survival.BMC bioinformatics · 2021Article
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- Perspectives on PARP inhibitors as pharmacotherapeutic strategies for breast cancer.Expert opinion on pharmacotherapy · 2021Review
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- A comprehensive analysis of somatic alterations in Chinese ovarian cancer patients.Scientific reports · 2021Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreased number of single nucleotide substitutions is seen in breast and ovarian cancer genomes carrying disease-associated mutations in BRCA1 or BRCA2. The significance of these genome-wide mutations is unknown. We hypothesize genome-wide mutation burden mirrors deficiencies in DNA repair and is associated with treatment outcome in ovarian cancer. METHODS AND
resultsThe total number of synonymous and non-synonymous exome mutations (Nmut), and the presence of germline or somatic mutation in BRCA1 or BRCA2 (mBRCA) were extracted from whole-exome sequences of high-grade serous ovarian cancers from The Cancer Genome Atlas (TCGA). Cox regression and Kaplan-Meier methods were used to correlate Nmut with chemotherapy response and outcome. Higher Nmut correlated with a better response to chemotherapy after surgery. In patients with mBRCA-associated cancer, low Nmut was associated with shorter progression-free survival (PFS) and overall survival (OS), independent of other prognostic factors in multivariate analysis. Patients with mBRCA-associated cancers and a high Nmut had remarkably favorable PFS and OS. The association with survival was similar in cancers with either BRCA1 or BRCA2 mutations. In cancers with wild-type BRCA, tumor Nmut was associated with treatment response in patients with no residual disease after surgery.
conclusionsTumor Nmut was associated with treatment response and with both PFS and OS in patients with high-grade serous ovarian cancer carrying BRCA1 or BRCA2 mutations. In the TCGA cohort, low Nmut predicted resistance to chemotherapy, and for shorter PFS and OS, while high Nmut forecasts a remarkably favorable outcome in mBRCA-associated ovarian cancer. Our observations suggest that the total mutation burden coupled with BRCA1 or BRCA2 mutations in ovarian cancer is a genomic marker of prognosis and predictor of treatment response. This marker may reflect the degree of deficiency in BRCA-mediated pathways, or the extent of compensation for the deficiency by alternative mechanisms.
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