ArticleGenome biology2014
Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution.
Article in Genome biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03979833 (Drivers of Hypoxia-induced Angiogenesis in Tumor Development), which is not on this map. Cited by 44 papers.
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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.
Drivers of Hypoxia-induced Angiogenesis in Tumor Development
Who cites it
44 citing papers in PubMed.
- Dynamic epigenetic changes to VHL occur with sunitinib in metastatic clear cell renal cancer.Oncotarget · 2016Trial
- Somatic mutational landscape in von Hippel-Lindau familial hemangioblastoma.Molecular oncology · 2026Article
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Integrative Clinical and Molecular Evaluation of Renal Cell Carcinoma with Merlin Protein Deficiency and Biallelic Loss of NF2.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- The mechanism of the PI3K-AKT-mTOR signaling pathway in renal cell carcinoma: current developments and future prospects.Frontiers in oncology · 2026Review
- VHL Gene Restoration Supports RCC Reprogramming to iPSCs but Does Not Ensure Line Stability.Cancers · 2025Article
- Intra- and inter-tumoural heterogeneity in von Hippel-Lindau disease-related renal cancer: a multimodal data study protocol.European radiology experimental · 2025Article
- von-Hippel Lindau and Hypoxia-Inducible Factor at the Center of Renal Cell Carcinoma Biology.Hematology/oncology clinics of North America · 2023Review
- Unraveling the Drivers of Tumorigenesis in the Context of Evolution: Theoretical Models and Bioinformatics Tools.Journal of molecular evolution · 2023Review
- Comprehensive Genomic Profiling of NF2-Mutated Kidney Tumors Reveals Potential Targets for Therapy.The oncologist · 2023Article
- Cell Adaptive Fitness and Cancer Evolutionary Dynamics.Cancer informatics · 2023Article
- Uncovering novel mutational signatures byCell genomics · 2022Article
- Review
- Involvement of PBRM1 in VHL disease-associated clear cell renal cell carcinoma and its putative relationship with the HIF pathway.Oncology letters · 2021Article
- Clonal Evolution of Multiple Myeloma-Clinical and Diagnostic Implications.Diagnostics (Basel, Switzerland) · 2021Review
- Molecular and Metabolic Subtypes in Sporadic and Inherited Clear Cell Renal Cell Carcinoma.Genes · 2021Review
- HPV+ oropharyngeal squamous cell carcinomas from patients with two tumors display synchrony of viral genomes yet discordant mutational profiles and signatures.Carcinogenesis · 2021Article
- Genetic Alterations in Renal Cancers: Identification of The Mechanisms Underlying Cancer Initiation and Progression and of Therapeutic Targets.Medicines (Basel, Switzerland) · 2020Review
- Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma.Cell stress · 2020Article
- A Pilot Study of Baseline Spatial Genomic Heterogeneity in Primary Gastric Cancers Using Multi-Region Endoscopic Sampling.Frontiers in oncology · 2020Article
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Authors and funding
35 authors.
Funding
Abstract
backgroundGenomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution.
resultsWe perform whole exome sequencing on four clear cell renal cell carcinomas removed from both kidneys of a patient with a germline VHL mutation. We report that tumors arising in this context are clonally independent and harbour distinct secondary events exemplified by loss of chromosome 3p, despite an identical genetic background and tissue microenvironment. We propose that divergent mutational and copy number anomalies are contingent upon the nature of 3p loss of heterozygosity occurring early in tumorigenesis. However, despite distinct 3p events, genomic, proteomic and immunohistochemical analyses reveal evidence for convergence upon the PI3K-AKT-mTOR signaling pathway. Four germline tumors in this young patient, and in a second, older patient with VHL syndrome demonstrate minimal intra-tumor heterogeneity and mutational burden, and evaluable tumors appear to follow a linear evolutionary route, compared to tumors from patients with sporadic clear cell renal cell carcinoma.
conclusionsIn tumors developing from a germline VHL mutation, the evolutionary principles of contingency and convergence in tumor development are complementary. In this small set of patients with early stage VHL-associated tumors, there is reduced mutation burden and limited evidence of intra-tumor heterogeneity.
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