Journal article
Clinical and Genomic Features of Patients with Renal Cell Carcinoma and Advanced Chronic Kidney Disease: Analysis of a Multi-Institutional Database
Cancers, Vol.16(10), 1920
01/01/2024
DOI: 10.3390/cancers16101920
PMCID: PMC11119962
PMID: 38791999
Abstract
Simple SummaryDespite the increased risk of developing renal cell carcinoma (RCC) in patients with advanced chronic kidney disease (ACKD), little is known about the patient clinical characteristics and genetic mutations found in these RCC tumors. Using a multi-institutional research network, this study compiled clinical records and somatic tumor whole exome sequencing data of 296 adult patients with RCC, 61 of whom had ACKD. Patients with RCC and ACKD were more likely to be male, present with earlier stage RCC at diagnosis, and have lower rates of BAP1 mutations. Median overall survival was not reached in either group over a median follow-up of 31.3 months. These findings suggest RCC in patients with ACKD develops via a BAP1-independent mutational driver and further support BAP1 loss as a marker of disease aggressiveness.AbstractBackground: Patients with advanced chronic kidney disease (ACKD) are at an increased risk of developing renal cell carcinoma (RCC), but molecular alterations in RCC specimens arising from ACKD and overall survival (OS) in affected patients are not well defined. Patients and Methods: Using the Oncology Research Information Exchange Network (ORIEN) Total Cancer Care® protocol, 296 consented adult patients with RCC and somatic tumor whole exome sequencing were included. Patients with ACKD were defined as those with serum creatinine ≥1.5 mg/dL prior to RCC diagnosis. Results: Of 296 patients with RCC, 61 met the criteria for ACKD. The most common somatic mutations in the overall cohort were in VHL (126, 42.6%), PBRM1 (102, 34.5%), and SETD2 (54, 18.2%). BAP1 had a decreased mutational frequency in RCC specimens from patients without ACKD as compared to those with ACKD (10.6% versus 1.6%), but this was not statistically significant in univariable (OR 0.14, p = 0.056) or multivariable (OR 0.15, p = 0.067) analysis. Median OS was not reached in either cohort. Conclusions: Using the clinicogenomic ORIEN database, our study found lower rates of BAP1 mutations in RCC specimens from patients with ACKD, which may reflect a BAP1-independent mutational driver of RCC in patients with ACKD.
Details
- Title: Subtitle
- Clinical and Genomic Features of Patients with Renal Cell Carcinoma and Advanced Chronic Kidney Disease: Analysis of a Multi-Institutional Database
- Creators
- Corbin Eule - University of Colorado Cancer CenterJunxiao Hu - University of Colorado Cancer CenterDale HedgesAlkesh Jani - University of Colorado Anschutz Medical CampusThomas Pshak - University of Colorado Anschutz Medical CampusBrandon Manley - Moffitt Cancer CenterAlejandro Sanchez - University of UtahRobert Dreicer - University of VirginiaZin Myint - Markey Cancer CenterYousef Zakharia - University of IowaElaine Lam - University of Colorado Cancer Center
- Resource Type
- Journal article
- Publication Details
- Cancers, Vol.16(10), 1920
- Publisher
- MDPI AG
- DOI
- 10.3390/cancers16101920
- PMID
- 38791999
- PMCID
- PMC11119962
- eISSN
- 2072-6694
- Language
- English
- Date published
- 01/01/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984628215502771
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