Abstract
BackgroundThis study aimed to assess the feasibility of a pan-cancer panel assay for high-risk renal cell carcinoma (RCC) in the Korean population. We also analyzed the clinical and genetic factors contributing to metastasis in clear cell RCC.MethodsThirty-one patients with advanced RCC who underwent radical nephrectomy were analyzed. A 1.8 Mb multi-cancer panel (including 25 RCC-related genes, such as VHL, PBRM1, SETD2, and MET), comprising 181 target genes, 23 fusion genes, and 45 drug target lesions developed by Seoul National University Hospital, was used for this study.ResultsWe extracted DNA from 30 of the 31 (96.7%) RCC specimens. Twenty-one patients (average age 63.3 ± 11.3 years) with clear cell RCC, 5 with papillary RCC, 3 with chromophobe RCC, and one patient, each with MiT family translocation carcinoma RCC and succinate dehydrogenase deficiency RCC, were analyzed. The sequencing depth was 430.8 ± 206.6 and 97 mutations (7.3 ± 2.7 mutations per patient) were detected. The most commonly mutated genes were VHL (46%), PBRM1 (30%), and BAP1, NOTCH4, and POLQ (23.33% each). Compared with TNM stage matched data from TCGA of clear cell RCC, VHL and PBRM1 are most common in both cohorts. Univariate and multivariate analyses revealed that tumor size (Hazard ratio = 2.47, p = 0.04) and PBRM1 (Hazard ratio = 28.69, p = 0.05) were related to metastasis in clear cell RCC.ConclusionThe pan-cancer panel comprised of RCC-related genes is a feasible and promising tool to evaluate genetic alterations in advanced RCC. However, large-scale studies and a focus on the clinical utility of this cancer panels is needed.
Highlights
This study aimed to assess the feasibility of a pan-cancer panel assay for high-risk renal cell carcinoma (RCC) in the Korean population
Renal cell carcinoma (RCC) is a malignancy that arises in the nephron tubules and has very heterogeneous histologic and clinical manifestations, accounting for approximately 90% of all cases of kidney cancer and 2.4% of all adult tumors [1]
The driver mutation of each subtype, such as von Hippel-Lindau (VHL), PBRM1, and BRCA-1 associated tumor protein 1 (BAP1) in Clear cell RCC (ccRCC); MET and fumarate hydratase (FH) in papillary RCC (pRCC); and phosphatase and tensin homolog (PTEN) or TP53 in chromophobe RCC (chrRCC); as well as the mutations related to prognosis, such as BAP1, PBRM1, or SET domain-containing 2 (SETD2) in ccRCC and cyclin-dependent kinase inhibitor 2A (CDKN2A) in pRCC have been identified in numerous next-generation sequencing (NGS) studies [7]
Summary
This study aimed to assess the feasibility of a pan-cancer panel assay for high-risk renal cell carcinoma (RCC) in the Korean population. We analyzed the clinical and genetic factors contributing to metastasis in clear cell RCC. Renal cell carcinoma (RCC) is a malignancy that arises in the nephron tubules and has very heterogeneous histologic and clinical manifestations, accounting for approximately 90% of all cases of kidney cancer and 2.4% of all adult tumors [1]. In the era of precision medicine, determining the molecular alteration in each RCC by NGS analysis is essential for diagnosis and treatment planning. Asian data have been limited in previously conducted large-scale NGS studies [8] and the histologic subtype and clinical behavior of RCC can differ among races [9].
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