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• W4361946159 abstract "<div>Abstract<p><b>Purpose:</b> Sarcomatoid renal cell carcinoma (SRCC) ranks among the most aggressive clinicopathologic phenotypes of RCC. However, the paucity of high-quality, genome-wide molecular examinations of SRCC has hindered our understanding of this entity.</p><p><b>Experimental Design:</b> We interrogated the mutational, copy number, and transcriptional characteristics of SRCC and compared these data with those of nonsarcomatoid RCC (RCC). We evaluated whole-exome sequencing, single-nucleotide polymorphism, and RNA sequencing data from patients with SRCC (<i>n</i> = 65) and RCC (<i>n</i> = 598) across different parent RCC subtypes, including clear-cell RCC, papillary RCC, and chromophobe RCC subtypes.</p><p><b>Results:</b> SRCC was molecularly discrete from RCC and clustered according to its parent RCC subtype, though with upregulation of TGFβ signaling across all subtypes. The epithelioid (E-) and spindled (S-) histologic components of SRCC did not show differences in mutational load among cancer-related genes despite a higher mutational burden in S-. Notably, sarcomatoid clear-cell RCC (SccRCC) showed significantly fewer deletions at 3p21-25, a lower rate of two-hit loss for <i>VHL</i> and <i>PBRM1</i>, and more mutations in <i>PTEN</i>, <i>TP53</i>, and <i>RELN</i> compared with ccRCC. A two-hit loss involving <i>VHL</i> predicted for ccRCC and a better prognosis, whereas mutations in <i>PTEN</i>, <i>TP53</i>, or <i>RELN</i> predicted for SccRCC and worse prognosis.</p><p><b>Conclusions:</b> SRCC segregates by parent subtype, and SccRCC has a fundamentally different early molecular pathogenesis, usually lacking the classic 3p21-25 deletion and showing distinctive mutational and transcriptional profiles. These features prompt a more precise molecular classification of RCC, with diagnostic, prognostic, and therapeutic implications. <i>Clin Cancer Res; 23(21); 6686–96. ©2017 AACR</i>.</p><p><i>See related commentary by Bergerot et al., p. 6381</i></p></div>" @default.
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• W4361946159 date "2023-03-31" @default.
• W4361946159 modified "2023-09-26" @default.
• W4361946159 title "Data from Sarcomatoid Renal Cell Carcinoma Has a Distinct Molecular Pathogenesis, Driver Mutation Profile, and Transcriptional Landscape" @default.
• W4361946159 doi "https://doi.org/10.1158/1078-0432.c.6526818" @default.
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