ArticleJournal of proteome research2017
Targeted Proteomic Analyses of Histone H4 Acetylation Changes Associated with Homologous-Recombination-Deficient High-Grade Serous Ovarian Carcinomas.
Article in Journal of proteome research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Ovarian cancer ascites proteomic profile reflects metabolic changes during disease progression.Biochemistry and biophysics reports · 2024Article
- Multifaceted Influence of Histone Deacetylases on DNA Damage Repair: Implications for Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2023Review
- Toward More Comprehensive Homologous Recombination Deficiency Assays in Ovarian Cancer, Part 1: Technical Considerations.Cancers · 2022Review
- Lamin post-translational modifications: emerging toggles of nuclear organization and function.Trends in biochemical sciences · 2021Review
- Proteogenomic Characterization of Ovarian HGSC Implicates Mitotic Kinases, Replication Stress in Observed Chromosomal Instability.Cell reports. Medicine · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Approximately 20% of high-grade serous ovarian cancers are homologous-recombination (HR)-deficient due to genetic and epigenetic mutations of HR pathway genes including the tumor suppressor genes BRCA1 and 2. HR deficiency (HRD) compromises cells' ability to efficiently repair DNA damage, but it also increases sensitivity to chemotherapeutic treatment strategies; however, not all ovarian cancer patients with HRD tumors exhibit positive responses to chemotherapy. Our previous iTRAQ-based comprehensive proteomic characterization of high-grade serous ovarian carcinomas found that lower levels of histone H4 acetylation at Lys12 and Lys16 (H4-K12acK16ac) were associated with HRD tumors compared with non-HRD tumors. In the current study, we developed and validated an H4-K12acK16ac parallel-reaction-monitoring (PRM)-targeted mass-spectrometry-based assay to analyze acetylation changes of histone H4 and to determine the association of these changes with total H4, histone acetyltransferase, and histone deacetylase (HDAC) levels. Whereas the levels of H4 and histone acetyltransferases were stable irrespective of HRD status, the levels of histone H4 acetylation and one HDAC, HDAC6, were elevated in the HRD tumors. Relative H4 acetylation levels were also analyzed by an antibody-based approach in additional ovarian tumors. It is possible that specific H4 acetylation at Lys12 and Lys16 associated with HRD could inform chemotherapeutic treatment modalities to improve ovarian cancer patients' treatment response.
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