Abstract | BACKGROUND: METHODS: We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. RESULTS: Types 1 and 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into 3 individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase. CONCLUSIONS: Types 1 and 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CpG island methylator phenotype in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least 3 subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).
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Authors | Byron H Lee |
Journal | Urologic oncology
(Urol Oncol)
Vol. 35
Issue 9
Pg. 578-579
(09 2017)
ISSN: 1873-2496 [Electronic] United States |
PMID | 28780132
(Publication Type: Journal Article, Comment)
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Copyright | Copyright © 2017 Elsevier Inc. All rights reserved. |
Topics |
- Carcinoma, Renal Cell
(genetics, pathology)
- Humans
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