Background: Accumulating evidence suggests that alternative RNA splicing has an important role in cancer development and progression by driving the expression of a diverse array of RNA and protein isoforms from a handful of genes. However, our understanding of the clinical significance of cancer-specific RNA splicing in renal cell carcinoma (RCC) is limited.
Objective: To characterize and validate a novel oncogene RNA splicing event discovered in patients with RCC and to correlate expression with clinical outcomes.
Design, Setting, And Participants: Using DNA and RNA sequencing, we identified a novel epidermal growth factor receptor (EGFR) splicing alteration (EGFR_pr20CTF) in RCC tumor tissue.
Outcome Measurements And Statistical Analysis: We confirmed the frequency and specificity of the EGFR_pr20CTF variant by analyzing cohorts of patients from our institution (n = 699) and The Cancer Genome Atlas (TCGA; n = 832). Furthermore, we analyzed its expression in tumor tissue and a human kidney cancer cell line using reverse transcriptase-polymerase chain reaction. Variant expression was also correlated with survival and response to systemic therapy.
Results And Limitations: EGFR_pr20CTF expression was identified in 71.7% (n = 71/99) of patients with RCC in our institutional cohort and in 56.7% (n = 279/492) of patients in the TCGA cohort. EGFR_pr20CTF was found to be specific to clear cell renal cell carcinoma (ccRCC), occurring in <0.2% of non-RCC tumors (n = 2/1091). High levels of EGFR_pr20CTF correlated with lower survival at 48 mo following immunotherapy (p = 0.036). The average survival in patients with high EGFR_pr20CTF expression was <16 mo.
Conclusions: The EGFR_pr20CTF RNA splice variant occurs frequently, is specific to patients with advanced ccRCC, and is associated with a poor response to immunotherapy.
Patient Summary: Cancer-specific RNA alternative splicing may portend a poor prognosis in patients with advanced clear cell renal cell carcinoma. Further investigation will help clarify whether EGFR_pr20CTF can be used as a biomarker for this patient population.
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http://dx.doi.org/10.1016/j.euf.2019.12.001 | DOI Listing |
Sci Rep
December 2024
Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, ShinjukuKu, Tokyo, 1608582, Japan.
Trends Biotechnol
December 2024
Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, València, Spain; Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n 46022, Valencia, Spain; CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, 28029, Madrid, Spain; Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Valencia, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, Avenida Eduardo Primo Yúfera, 3, 46012, Valencia, Spain; Unidad Mixta de Investigación en Nanomedicina y Sensores, Universitat Politècnica de València, Instituto de Investigación Sanitaria La Fe (IISLAFE), Avenida Fernando Abril Martorell, 106, 46026, Valencia, Spain.
The demand for novel, minimally invasive, cost-effective, and easily readable diagnostic tools, primarily designed for the longitudinal monitoring of diseases and their treatments, has promoted the development of diagnostic systems that selectively target cells, tissues, or organs, at the same time minimizing their nonspecific accumulation, thus reducing the risk of toxicity and side effects. In this review, we explore the development of renal-clearable systems in non-invasive or minimally invasive detection protocols, all with the objective of minimizing nonspecific accumulation and its associated toxicity effects through quick renal excretion. These probes can identify molecules of interest or different healthy states of the patients through the direct analysis of urine (urinalysis).
View Article and Find Full Text PDFIn Vivo
December 2024
Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece;
Background/aim: Clear cell renal cell carcinoma (ccRCC) represents the most common type of renal cancer. When resectable, nephrectomy is the only radical treatment for ccRCC, however metastasis is already present at 30% of the patient population. Although great progress has been made in the field of targeted therapy with the emergence of immune checkpoint inhibitors (ICIs) the cure of metastatic ccRCC (mccRCC) remains far from achieved.
View Article and Find Full Text PDFAnticancer Res
January 2025
Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Background/aim: Immuno-oncology (IO) improves the prognosis of advanced renal cell carcinoma (RCC). Since research has so far been limited to clinical trials, we herein focused on the effects of IO-tyrosine kinase inhibitor (TKI) combination therapy in real-world clinical settings.
Patients And Methods: We conducted a retrospective study on 125 patients with advanced RCC who received IO-TKI combination therapy or TKI monotherapy.
J Med Genet
December 2024
John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Introduction: Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disorder classically associated with multiple basal cell carcinomas, odontogenic keratocysts and skeletal anomalies. However, its significant phenotypic heterogeneity often delays the diagnosis. Here, we undertake the first comprehensive characterisation of NBCCS and congenital urinary tract anomalies.
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