Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets Journal Article
| Authors: | Chen, Y. B.; Xu, J.; Skanderup, A. J.; Dong, Y.; Brannon, A. R.; Wang, L.; Won, H. H.; Wang, P. I.; Nanjangud, G. J.; Jungbluth, A. A.; Li, W.; Ojeda, V.; Hakimi, A. A.; Voss, M. H.; Schultz, N.; Motzer, R. J.; Russo, P.; Cheng, E. H.; Giancotti, F. G.; Lee, W.; Berger, M. F.; Tickoo, S. K.; Reuter, V. E.; Hsieh, J. J. |
| Article Title: | Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets |
| Abstract: | Renal cell carcinomas with unclassified histology (uRCC) constitute a significant portion of aggressive non-clear cell renal cell carcinomas that have no standard therapy. The oncogenic drivers in these tumours are unknown. Here we perform a molecular analysis of 62 high-grade primary uRCC, incorporating targeted cancer gene sequencing, RNA sequencing, single-nucleotide polymorphism array, fluorescence in situ hybridization, immunohistochemistry and cell-based assays. We identify recurrent somatic mutations in 29 genes, including NF2 (18%), SETD2 (18%), BAP1 (13%), KMT2C (10%) and MTOR (8%). Integrated analysis reveals a subset of 26% uRCC characterized by NF2 loss, dysregulated Hippo-YAP pathway and worse survival, whereas 21% uRCC with mutations of MTOR, TSC1, TSC2 or PTEN and hyperactive mTORC1 signalling are associated with better clinical outcome. FH deficiency (6%), chromatin/DNA damage regulator mutations (21%) and ALK translocation (2%) distinguish additional cases. Altogether, this study reveals distinct molecular subsets for 76% of our uRCC cohort, which could have diagnostic and therapeutic implications. © The Author(s) 2016. |
| Journal Title: | Nature Communications |
| Volume: | 7 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2016-10-07 |
| Start Page: | 13131 |
| Language: | English |
| DOI: | 10.1038/ncomms13131 |
| PROVIDER: | scopus |
| PMCID: | PMC5059781 |
| PUBMED: | 27713405 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2016 -- Source: Scopus |
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