ArticleMolecular oncology2016
Spatial and temporal clonal evolution during development of metastatic urothelial carcinoma.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Urinary Biomarkers in Urological Oncology: From Biological Origin to Clinical Decision-Making-A Narrative Review.Diagnostics (Basel, Switzerland) · 2026Review
- Clinicopathological characteristics and prognostic significance of HER2 status evaluation in patients with urothelial carcinoma: a retrospective single-center experience in China.Virchows Archiv : an international journal of pathology · 2026Article
- Abscopal effect induced by conventional fractionated radiotherapy following anti-PD-1 immunotherapy in pulmonary metastatic thymic squamous cell carcinoma: a case report and literature review.Frontiers in immunology · 2026Review
- Fecal microbiota transplantation: a novel strategy and challenges in the adjuvant treatment of bladder Cancer.Frontiers in microbiology · 2026Review
- Bladder cancer subtypes exhibit limited plasticity across different microenvironments and in metastases.Experimental hematology & oncology · 2025Article
- Pre-treatment metastatic biopsy: a step towards precision oncology for urothelial cancer.Nature reviews. Urology · 2025Review
- Molecular and clonal evolutioniScience · 2023Article
- Assessment of aggressive bladder cancer mutations in plasma cell-free DNA.Frontiers in oncology · 2023Article
- DNMT3A/Cancers · 2022Article
- Urothelial Bladder Carcinomas with High Tumor Mutation Burden Have a Better Prognosis and Targetable Molecular Defects beyond Immunotherapies.Current oncology (Toronto, Ont.) · 2022Article
- [Molecular diagnostics of bladder cancer-practical ramifications].Der Urologe. Ausg. A · 2021Article
- Molecular Pathology of Urothelial Carcinoma.Surgical pathology clinics · 2021Review
- Therapeutic and prognostic implications of NOTCH and MAPK signaling in bladder cancer.Cancer science · 2021Article
- Tumor heterogeneity and the potential role of liquid biopsy in bladder cancer.Cancer communications (London, England) · 2021Review
- Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis.Nature communications · 2020Article
- Genomic heterogeneity in bladder cancer: challenges and possible solutions to improve outcomes.Nature reviews. Urology · 2020Review
- The risk of oversimplification in risk-stratification of neoadjuvant chemotherapy-responses in muscle invasive bladder cancer.Translational andrology and urology · 2019Article
- Discordant molecular subtype classification in the basal-squamous subtype of bladder tumors and matched lymph-node metastases.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2018Article
- Treatment resistance in urothelial carcinoma: an evolutionary perspective.Nature reviews. Clinical oncology · 2018Review
- Low Frequency of Intratumor Heterogeneity in Bladder Cancer Tissue Microarrays.Bladder cancer (Amsterdam, Netherlands) · 2018Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with metastatic bladder cancer have a median survival of only 13-14 months. Precision medicine using targeted therapy may improve survival. Here we investigated spatial and temporal tumour evolution and tumour heterogeneity in order to evaluate the potential use of targeted treatment of metastatic bladder cancer. We performed a proof-of-concept study by whole exome sequencing of multiple tumour regions (n = 22) from three patients with metastatic bladder cancer. DNA from primary and metastatic tumour biopsies was analysed for mutations using Mutect and potential therapeutic targets were identified. We identified 256, 265 and 378 somatic mutations per patient, encompassing mutations with an estimated functional impact in 6-12 known disease driver genes per patient. Disease driver mutations present in all tumour regions could be identified in all cases, however, over time metastasis specific driver mutations emerged. For each patient we identified 6-10 potentially therapeutic targets, however very few targets were present in all regions. Low mutational allele frequencies were observed in most regions suggesting a complex mixture of different cancer cells with no spatial demarcation of subclones. In conclusion, primary bladder tumours and metastatic lesions showed heterogeneity at the molecular level, but within the primary tumour the heterogeneity appeared low. The observed lack of potential therapeutic targets common to all cancer cells in primary tumours and metastases emphasizes the challenges in designing rational targeted therapy solely based on analysis of the primary tumours.
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Registered trials
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