ArticleProceedings of the National Academy of Sciences of the United States of America2016
Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Prognostic Significance of Sarcomatoid Differentiation in Patients With Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2020Pooled it
- Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma.Nature communications · 2021Trial
- A multicenter, prospective phase II trial of gemcitabine plus axitinib in patients with renal cell carcinoma with a predominant sarcomatoid component.Investigational new drugs · 2019Trial
- Transcriptomic Profiling of the Tumor Microenvironment Reveals Distinct Subgroups of Clear Cell Renal Cell Cancer: Data from a Randomized Phase III Trial.Cancer discovery · 2019Trial
- A randomized phase 2 study of MK-2206 versus everolimus in refractory renal cell carcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- Repurposing Seleno-L-Methionine as a Pleiotropic Immunomodulatory Agent to Overcome TGF-β1/HIF-Driven Immune Evasion in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Translational Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Renal cell carcinoma: molecular understanding and therapeutic development.Cell death and differentiation · 2026Review
- Sarcomatoid Renal Cell Carcinoma: A Clinical Review.Diagnostics (Basel, Switzerland) · 2026Review
- Targeting PLOD2 induces epithelioid differentiation and improves therapeutic response in sarcomatoid renal cell carcinoma.Journal of advanced research · 2026Article
- Integration of scRNA-Seq and scATAC-Seq Reveals Malignant Characteristics of Sarcomatoid Clear Cell Renal Cell Carcinoma.Cancer science · 2025Article
- Comprehensive tumor-immune profiling reveals mediators of paradoxical immune sensitivity in sarcomatoid renal cell carcinoma.Cancer cell · 2025Article
- Molecular and therapeutic landscape of non-clear cell renal carcinoma.Nature reviews. Urology · 2025Review
- Review
- Chromophobe renal cell carcinoma with sarcomatoid change: A case report.Oncology letters · 2025Article
- Identifying potential risk genes for clear cell renal cell carcinoma with deep reinforcement learning.Nature communications · 2025Article
- A novel multigene panel (Sig27) robustly predicts poor prognosis of renal cell carcinoma via high-level associations with immunosuppressive features.BJC reports · 2025Article
- Identification of LIMK1 as a biomarker in clear cell renal cell carcinoma: from data mining to validation.Journal of cancer research and clinical oncology · 2025Article
- Trends and Outcomes in Sarcomatoid Renal Cell Carcinoma: Analysis of the National Cancer Data Base.European urology open science · 2025Article
- Toripalimab in combination with chemotherapy effectively suppresses local recurrence and metastatic sarcomatoid renal cell carcinoma: A case report.World journal of clinical cases · 2024Article
- Molecular profile of bladder cancer progression to clinically aggressive subtypes.Nature reviews. Urology · 2024Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
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Funding
Abstract
The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers.
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