SET-domain containing 2 (SETD2) and BRCA1-associated protein 1 (BAP1), both chromatin remodeling genes, are frequently mutated in clear cell renal cell carcinoma (ccRCC) and involved in tumor progression and metastasis. Herein, we studied clinicopathologic features of 7 cases of locally advanced ccRCC with single SETD2 mutation, and compared to 7 cases of locally advanced ccRCC with single BAP1 mutation. SETD2-mutated ccRCC showed high-grade transformation, comprising of enlarged tumor cells with voluminous clear cytoplasm, enlarged irregular nuclei with prominent nucleoli, eosinophilic cytoplasmic granules, arranged in various architectural patterns such as large nested, tubular, tubulopapillary and solid. 71 % (5 of 7 cases) of SETD2-mutated ccRCC showed a rhabdoid morphology. SETD2-mutated ccRCC have striking propensity for invasive growth; all cases have vascular invasion and perirenal (extracapsular) adipose tissue invasion. After nephrectomy, distant metastasis was found in 67 % (4 of 7 cases) of patients with SETD2-mutated ccRCC. The most common metastatic site was the lung (3 cases), followed by precaval lymph nodes (1 case). BAP1-mutated ccRCC also showed a similar high-grade morphology, with rhabdoid and/or sarcomatoid features. Their high-grade features mostly overlapped with those of SETD2-mutated ccRCC, which makes difficult to predict the presence of BAP1 or SETD2 mutation solely from morphology. These findings justify the use of molecular testing to detect these mutations, especially when we encounter high-grade ccRCC. Detecting SETD2 and BAP1 mutation in ccRCC is useful for risk stratification and proper therapeutic strategy.
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http://dx.doi.org/10.1016/j.anndiagpath.2023.152223 | DOI Listing |
Background: Renal cell carcinoma (RCC) is the most prevalent type of malignant kidney tumor in adults, with clear cell renal cell carcinoma (ccRCC) comprising about 75% of all cases. The SETD2 gene, which is involved in the modification of histone proteins, is often found to have alterations in ccRCC. Yet, our understanding of how these SETD2 mutations affect ccRCC characteristics and behavior within the tumor microenvironment is still not fully understood.
View Article and Find Full Text PDFAnn Diagn Pathol
February 2024
Department of Pathology, Genitourinary Pathology Center of Excellence, University of Pittsburgh Medical Center, Pittsburgh, USA.
Kidney Cancer J
November 2022
Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Background: SET domain-containing protein 2 () is commonly mutated in renal cell carcinoma. SETD2 methylates histone H3 as well as a growing list of non-histone proteins.
Objective: Initially, we sought to explore SETD2-dependent changes in lysine methylation of proteins in proximal renal tubule cells.
J BUON
January 2016
Department of Urology, Jiangxi Pingxiang People's Hospital, Jiangxi 337055, P.R. China.
Expert Rev Mol Diagn
May 2016
a 1 Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona, Italy.
Several novel recurrent mutations of histone modifying and chromatin remodeling genes have been identified in renal cell carcinoma. These mutations cause loss of function of several genes located in close proximity to VHL and include PBRM1, BAP1 and SETD2. PBRM1 encodes for BAF180, a component of the SWI/SNF chromatin remodeling complex, and is inactivated in, on average, 36% of clear cell renal cell carcinoma (ccRCC).
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