ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Whole-exome sequencing of muscle-invasive bladder cancer identifies recurrent mutations of UNC5C and prognostic importance of DNA repair gene mutations on survival.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04872036 (Investigation of Prognostic Biomarkers in Patients With Urothelial Carcinoma Treated With Platinum Regimens), which is not on this map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Investigation of Prognostic Biomarkers in Patients With Urothelial Carcinoma Treated With Platinum Regimens
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- PARP Inhibitors for Metastatic Urothelial Carcinoma: A Systematic Review of Efficacy and Safety.Bladder cancer (Amsterdam, Netherlands) · 2023Pooled it
- A Randomized, Double-Blind, Biomarker-Selected, Phase II Clinical Trial of Maintenance Poly ADP-Ribose Polymerase Inhibition With Rucaparib Following Chemotherapy for Metastatic Urothelial Carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit From PD-1/PD-L1 Blockade in Advanced Urothelial Cancers.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Afatinib Activity in Platinum-Refractory Metastatic Urothelial Carcinoma in Patients With ERBB Alterations.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Trial
- Netrin-1 signaling pathway mechanisms in neurodegenerative diseases.Neural regeneration research · 2025Article
- Biomarkers for predicting bladder cancer therapy response.Oncology research · 2025Review
- Contemporary Molecular Markers for Predicting Systemic Treatment Response in Urothelial Bladder Cancer: A Narrative Review.Cancers · 2024Review
- Research progress of the netrins and their receptors in cancer.Journal of cellular and molecular medicine · 2024Review
- H3 histone methylation landscape in male urogenital cancers: from molecular mechanisms to epigenetic biomarkers and therapeutic targets.Frontiers in cell and developmental biology · 2023Review
- Genomics and Immunomics in the Treatment of Urothelial Carcinoma.Current oncology (Toronto, Ont.) · 2022Review
- Association between pathogenic germline mutations in BRCA2 and ATM and tumor-infiltrating lymphocytes in primary prostate cancer.Cancer immunology, immunotherapy : CII · 2022Article
- Comprehensive genomic profiling of upper tract urothelial carcinoma and urothelial carcinoma of the bladder identifies distinct molecular characterizations with potential implications for targeted therapy & immunotherapy.Frontiers in immunology · 2022Article
- Molecular markers of systemic therapy response in urothelial carcinoma.Asian journal of urology · 2021Review
- Immunogenomics in personalized cancer treatments.Journal of human genetics · 2021Review
- Mutations ofJournal of clinical and translational research · 2021Article
- Recurrent PALB2 mutations and the risk of cancers of bladder or kidney in Polish population.Hereditary cancer in clinical practice · 2021Article
- Transcriptome-Wide Map of NFrontiers in oncology · 2021Article
- Genomic profiling reveals high frequency of DNA repair genetic aberrations in gallbladder cancer.Scientific reports · 2020Article
- Alterations of DNA damage repair in cancer: from mechanisms to applications.Annals of translational medicine · 2020Review
- Tumor mutation burden in Chinese cancer patients and the underlying driving pathways of high tumor mutation burden across different cancer types.Annals of translational medicine · 2020Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeBecause of suboptimal outcomes in muscle-invasive bladder cancer even with multimodality therapy, determination of potential genetic drivers offers the possibility of improving therapeutic approaches and discovering novel prognostic indicators. EXPERIMENTAL
designUsing pTN staging, we case-matched 81 patients with resected ≥pT2 bladder cancers for whom perioperative chemotherapy use and disease recurrence status were known. Whole-exome sequencing was conducted in 43 cases to identify recurrent somatic mutations and targeted sequencing of 10 genes selected from the initial screening in an additional 38 cases was completed. Mutational profiles along with clinicopathologic information were correlated with recurrence-free survival (RFS) in the patients.
resultsWe identified recurrent novel somatic mutations in the gene UNC5C (9.9%), in addition to TP53 (40.7%), KDM6A (21.0%), and TSC1 (12.3%). Patients who were carriers of somatic mutations in DNA repair genes (one or more of ATM, ERCC2, FANCD2, PALB2, BRCA1, or BRCA2) had a higher overall number of somatic mutations (P = 0.011). Importantly, after a median follow-up of 40.4 months, carriers of somatic mutations (n = 25) in any of these six DNA repair genes had significantly enhanced RFS compared with noncarriers [median, 32.4 vs. 14.8 months; hazard ratio of 0.46, 95% confidence interval (CI), 0.22-0.98; P = 0.0435], after adjustment for pathologic pTN staging and independent of adjuvant chemotherapy usage.
conclusionBetter prognostic outcomes of individuals carrying somatic mutations in DNA repair genes suggest these mutations as favorable prognostic events in muscle-invasive bladder cancer. Additional mechanistic investigation into the previously undiscovered role of UNC5C in bladder cancer is warranted.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.