Article ; Online: Intratumoral morphologic and molecular heterogeneity of rhabdoid renal cell carcinoma: challenges for personalized therapy.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
2015 Volume 28, Issue 9, Page(s) 1225–1235
Abstract: ... changes in rhabdoid clear-cell renal cell carcinoma. We macrodissected the rhabdoid and clear ... of rhabdoid clear-cell renal cell carcinoma (n=8) and non-rhabdoid clear-cell renal cell carcinoma (n=37) was ... Rhabdoid histology in clear-cell renal cell carcinoma is associated with a poor prognosis ...
| Abstract | Rhabdoid histology in clear-cell renal cell carcinoma is associated with a poor prognosis. The prognosis of patients with clear-cell renal cell carcinoma may also be influenced by molecular alterations. The aim of this study was to evaluate the association between histologic features and salient molecular changes in rhabdoid clear-cell renal cell carcinoma. We macrodissected the rhabdoid and clear-cell epithelioid components from 12 cases of rhabdoid clear-cell renal cell carcinoma. We assessed cancer-related mutations from eight cases using a clinical next-generation exome-sequencing platform. The transcriptome of rhabdoid clear-cell renal cell carcinoma (n=8) and non-rhabdoid clear-cell renal cell carcinoma (n=37) was assessed by RNA-seq and gene expression microarray. VHL (63%) showed identical mutations in all regions from the same tumor. BAP1 (38%) and PBRM1 (13%) mutations were identified in the rhabdoid but not in the epithelioid component and were mutually exclusive in 3/3 cases and 1 case, respectively. SETD2 (63%) mutations were discordant between different histologic regions in 2/5 cases, with mutations called only in the epithelioid and rhabdoid components, respectively. The transcriptome of rhabdoid clear-cell renal cell carcinoma was distinct from advanced-stage and high-grade clear-cell renal cell carcinoma. The diverse histologic components of rhabdoid clear-cell renal cell carcinoma, however, showed a similar transcriptomic program, including a similar prognostic gene expression signature. Rhabdoid clear-cell renal cell carcinoma is transcriptomically distinct and shows a high rate of SETD2 and BAP1 mutations and a low rate of PBRM1 mutations. Driver mutations in clear-cell renal cell carcinoma are often discordant across different morphologic regions, whereas the gene expression program is relatively stable. Molecular profiling of clear-cell renal cell carcinoma may improve by assessing for gene expression and sampling tumor foci from different histologic regions. |
|||||
|---|---|---|---|---|---|---|
| MeSH term(s) | Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/pathology ; DNA Mutational Analysis ; High-Throughput Nucleotide Sequencing ; Humans ; Kidney Neoplasms/genetics ; Kidney Neoplasms/pathology ; Laser Capture Microdissection ; Oligonucleotide Array Sequence Analysis ; Precision Medicine ; Transcriptome | |||||
| Language | English | |||||
| Publishing date | 2015-06-26 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 645073-8 | |||||
| ISSN | 1530-0285 ; 0893-3952 | |||||
| ISSN (online) | 1530-0285 | |||||
| ISSN | 0893-3952 | |||||
| DOI | 10.1038/modpathol.2015.68 | |||||
| Shelf mark |
|
|||||
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 2450: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.