ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Prevalence and Landscape of Actionable Genomic Alterations in Renal Cell Carcinoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of renal cell carcinoma, version 3.0.Journal for immunotherapy of cancer · 2026Guideline
- Dissecting the Tumor Microenvironment to Identify Biomarkers of Outcome to Anti-PD-1 Therapy in Clear-Cell Renal Cell Carcinoma: Analyses of the HCRN GU16-260 Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Integrated spatial and single‑cell transcriptomics maps disulfidptosis in renal cell carcinoma and reveals PDLIM1 as a prognostic biomarker and potential therapeutic target.Translational oncology · 2026Article
- OncoBERT: Context-Aware Modeling of Somatic Mutations for Precision Oncology.bioRxiv : the preprint server for biology · 2026Article
- Identification of Predictive Genomic Biomarkers in Metastatic Clear Cell Renal Cell Carcinoma: A Comprehensive Analysis of Real-World Clinicogenomic Data.JCO precision oncology · 2026Article
- MLH1 Mismatch Repair Deficiency Predicts Exceptional Response to Immune Checkpoint Inhibition in Clear-cell Renal Cell Carcinoma.European urology · 2025Article
- Precision Treatment of Metachronous Multiple Primary Malignancies Based on Constructing Patient Tumor-Derived Organoids.Biomedicines · 2024Article
- Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma.Discover oncology · 2024Article
- Altered cytoplasmic and nuclear ADP-ribosylation levels analyzed with an improved ADP-ribose binder are a prognostic factor in renal cell carcinoma.The journal of pathology. Clinical research · 2023Article
- Patient-derived organoids potentiate precision medicine in advanced clear cell renal cell carcinoma.Precision clinical medicine · 2022Article
- The germline mutational landscape of genitourinary cancers and its indication for prognosis and risk.BMC urology · 2022Article
- Matched Molecular Profiling of Cell-Free DNA and Tumor Tissue in Patients With Advanced Clear Cell Renal Cell Carcinoma.JCO precision oncology · 2022Article
- Long-Term Cardiac Disease- and Cancer-Associated Mortalities in Patients With Non-Metastatic Stomach Adenocarcinoma Receiving Resection and Chemotherapy: A Large Competing-Risk Population-Based Cohort Study.World journal of oncology · 2022Article
- Survival Prognosis, Tumor Immune Landscape, and Immune Responses of PPP1R18 in Kidney Renal Clear Cell Carcinoma and Its Potentially Double Mechanisms.World journal of oncology · 2022Article
- ERBB2 promoter demethylation and immune cell infiltration promote a poor prognosis for cancer patients.Frontiers in oncology · 2022Article
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Authors and funding
20 authors at 1 institution in 1 country.
Funding
Abstract
purposeWe report our experience with next-generation sequencing to characterize the landscape of actionable genomic alterations in renal cell carcinoma (RCC). EXPERIMENTAL
designA query of our institutional clinical sequencing database (MSK-IMPACT) was performed that included tumor samples from 38,468 individuals across all cancer types. Somatic variations were annotated using a precision knowledge database (OncoKB) and the available clinical data stratified by level of evidence. Alterations associated with response to immune-checkpoint blockade (ICB) were analyzed separately; these included DNA mismatch repair (MMR) gene alterations, tumor mutational burden (TMB), and microsatellite instability (MSI). Data from The Cancer Genome Atlas (TCGA) consortium as well as public data from several clinical trials in metastatic RCC were used for validation purposes. Multiregional sequencing data from the TRAcking Cancer Evolution through Therapy (TRACERx) RENAL cohort were used to assess the clonality of somatic mutations.
resultsOf the 753 individuals with RCC identified in the MSK-IMPACT cohort, 115 showed evidence of targetable alterations, which represented a prevalence of 15.3% [95% confidence interval (CI), 12.7%-17.8%). When stratified by levels of evidence, the alterations identified corresponded to levels 2 (11.3%), 3A (5.2%), and 3B (83.5%). A low prevalence was recapitulated in the TCGA cohort at 9.1% (95% CI, 6.9%-11.2%). Copy-number variations predominated in papillary RCC tumors, largely due to amplifications in the
conclusionsRCC harbors a low prevalence of clinically actionable alterations compared with other tumors and the evidence supporting their clinical use is limited. These aberrations were found to be more common in advanced disease and seem to occur later during tumor evolution. Our study provides new insights on the role of targeted therapies for RCC and highlights the need for additional research to improve treatment selection using genomic profiling.
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