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• W3041328884 abstract "Objectives To identify clear cell renal cell carcinoma‐related gene mutations potentially associated with aggressive disease, sarcomatoid differentiation or poor prognosis. Methods We carried out genomic analysis of 217 tumor foci from 25 patients with conventional clear cell renal cell carcinoma (14 patients), clear cell renal cell carcinoma with sarcomatoid differentiation (six patients) and non‐clear cell renal cell carcinoma (five patients). Each tumor nodule on the tissue block that corresponded to the same focus on the slide was separated from the normal parenchyma and other histologically distinct areas of tumor. The isolated tumor foci were used for subsequent analyses and sequencing. Deoxyribonucleic acid from the formalin‐fixed paraffin‐embedded tissues was extracted. Multiplex bar‐coded polymerase chain reaction amplification was carried out using next‐generation sequencing libraries. Results Overall, 67 protein alterations, including amino acid alterations, frame shifts and splice site mutations in seven genes were identified in the cohort of renal cell carcinoma tumors included in this study. Fewer patients with clear cell renal cell carcinoma with sarcomatoid differentiation had clear cell renal cell carcinoma‐related mutations in comparison with patients with conventional clear cell renal cell carcinoma. Additionally, the average number of unique clear cell renal cell carcinoma‐related protein alterations per patient was significantly lower in clear cell renal cell carcinoma with sarcomatoid differentiation than in conventional clear cell renal cell carcinoma. Mutations in PBRM1 were identified in a higher proportion of patients with high‐grade tumors (World Health Organization/International Society of Urological Pathology grade 4) and in the primary tumors of six of 10 (60%) patients with metastatic disease. Conclusions Although there are pitfalls due to intratumoral heterogeneity and sampling bias, mutations in PBRM1 may be associated with metastasis and aggressive disease in clear cell renal cell carcinoma." @default.
• W3041328884 created "2020-07-16" @default.
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• W3041328884 date "2020-07-08" @default.
• W3041328884 modified "2023-09-26" @default.
• W3041328884 title "Molecular characteristics and markers of advanced clear cell renal cell carcinoma: Pitfalls due to intratumoral heterogeneity and identification of genetic alterations associated with metastasis" @default.
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• W3041328884 doi "https://doi.org/10.1111/iju.14302" @default.
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