ArticleBMC cancer2021
RB1 and TP53 co-mutations correlate strongly with genomic biomarkers of response to immunity checkpoint inhibitors in urothelial bladder cancer.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- Evolving patterns of co-mutations from tumor initiation to metastatic progression.Nature genetics · 2026Article
- Comprehensive Genomic Characterization Between Urothelial Carcinoma Subtypes/Divergent Differentiation (S/DD) and Pure Urothelial Carcinoma Using a Large-Scale Japanese Genomic Panel Dataset.International journal of urology : official journal of the Japanese Urological Association · 2026Observational
- The Insulin-Urothelial Axis: Evaluating Insulin Resistance as a Convergent Driver of Bladder Cancer Across Diverse Risk Factor Profiles.International journal of molecular sciences · 2026Review
- Multi-omic profiling defines three distinct molecular subtypes of urothelial carcinoma with implications for precision therapy.Clinical and translational medicine · 2026Article
- Cell-of-origin and genetic drivers define advanced bladder cancer subtypes and potential therapeutic response in mouse models.Journal of experimental & clinical cancer research : CR · 2026Article
- Targeted therapies for urothelial carcinoma: From FGFR inhibitors to next‑generation antibody-drug conjugates (Review).International journal of oncology · 2026Review
- Characterization and clinical implications of CpG island methylator phenotypes of resistant tumors.Clinical epigenetics · 2026Article
- Integrated Genomic and Single-Cell Analysis Reveals Heterogeneity, Prognosis, and Treatment Vulnerability in Urothelial Carcinoma.Human mutation · 2026Article
- Effect of co-occurring mutations inFrontiers in immunology · 2026Article
- Rare Early Coexistence of Classic Urothelial and Small Cell Carcinoma of the Urinary Bladder.Case reports in urology · 2026Article
- Molecular and immune characteristics of neuroendocrine bladder carcinoma - Implications for diagnosis, prognosis, and therapy: A review.Biomolecules & biomedicine · 2025Review
- Genomic characterization of tumor mutational burden-high breast carcinomas.NPJ precision oncology · 2025Article
- Optimizing enfortumab vedotin plus pembrolizumab therapy.Oncotarget · 2025Review
- Pulsed Electromagnetic Field Therapy Alters the Genomic Profile of Bladder Cancer Cell Line HT-1197.Journal of personalized medicine · 2025Article
- Redefining bladder cancer treatment: innovations in overcoming drug resistance and immune evasion.Frontiers in immunology · 2025Review
- Bladder cancer biomarkers.Exploration of targeted anti-tumor therapy · 2025Review
- Characterization of cancer-related fibroblasts in bladder cancer and construction of CAFs-based bladder cancer classification: insights from single-cell and multi-omics analysis.Frontiers in immunology · 2025Article
- Contemporary Molecular Markers for Predicting Systemic Treatment Response in Urothelial Bladder Cancer: A Narrative Review.Cancers · 2024Review
- Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- The gut microbiome-prostate cancer crosstalk is modulated by dietary polyunsaturated long-chain fatty acids.Nature communications · 2024Article
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3 authors at 1 institution in 1 country.
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Abstract
backgroundMuscle invasive urothelial bladder carcinoma (MIBC) present RB1 and TP53 somatic alterations in a variable percentage of tumors throughout all molecular subtypes. MIBCs with neuroendocrine features have a high response rate to immunity checkpoint inhibitors (ICIs). Whether the presence of somatic co-alterations in these 2 genes in MIBCs is relevant to their responsiveness to ICIs is not known.
methodsThe potential correlation of different genomic biomarkers of response to ICIs like tumor mutational burden (TMB), single nucleotide variants (SNV) predicted neoantigens, DNA damage response (DDR) genes, DNA somatic signatures and TILs infiltrate was explored in patients with somatic co-alterations in RB1 and TP53 (RB1&TP53) as compared with patients with no alterations in any (double wild type, DWT) or with alterations in just one of the 2 genes. The Cancer Genome Atlas (TCGA) pancancer BLCA dataset of cystectomy specimens (n = 407) with mutation, copy number alterations and transcriptomic (RNA sequencing) data as well as the IMVigor 210 study (n = 348) of metastatic urothelial bladder cancers treated with atezolizumab (PD-L1 inhibitor) with clinical response data containing transcriptomic (RNA sequencing), along with a subset (n = 274) with mutation and copy number data were used for this purpose. A novel tumor microenvironment metascore (TMM) was developed based in a LASSO regularized Cox model with predictive and prognostic ability.
resultsSamples with co-altered RB1&TP53: a) were enriched in immunity effectors (CD8 cytotoxic lymphocytes, NK cells) and display higher scores of a T cell inflamed signature; b) have a higher TMB, higher number of SNV predicted neoantigens and higher TILs fractions; c) have a higher number of DDR mutated and deep deleted DDR genes; d) have DNA somatic signatures 2 and 13 related to APOBEC mutagenesis. Using the IMVigor 210 dataset, RB1&TP53 samples had the highest response rate to atezolizumab and a strong correlation with TMB and TMM. The consensus molecular subtype classification in the IMVigor 210 dataset showed a significant correlation with both the response to treatment (p = 0.001, Chisquare) and the presence of RB1 and TP53 genomic alterations (p < 0.001, Chisquare).
conclusionsRB1&TP53 co-alterations are strongly associated with genomic biomarkers of response to ICIs in MIBCs.
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