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https://doi.org/10.1038/ncomms13131
| Title: | Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets | 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 |
Keywords: | BAP1 protein DNA KMT2C protein mammalian target of rapamycin mammalian target of rapamycin complex 1 merlin oncoprotein phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase RNA SETD2 protein TSC1 protein tuberin unclassified drug BAP1 protein, human histone lysine methyltransferase MTOR protein, human Set2 protein, human target of rapamycin kinase tumor protein tumor suppressor protein ubiquitin thiolesterase bioassay cancer cells and cell components gene expression genetic analysis genetic marker histology molecular analysis mutation protein tumor Article cancer genetics cancer survival carcinogenesis cell assay chromatin clinical outcome controlled study DNA damage fluorescence in situ hybridization gene expression germline mutation histology human human cell human tissue immunohistochemistry kidney carcinoma molecular genetics nucleotide sequence RNA sequence signal transduction single nucleotide polymorphism somatic mutation tumor gene genetics HEK293 cell line kidney tumor neurofibromatosis type 2 pathology renal cell carcinoma tumor cell line Carcinoma, Renal Cell Cell Line, Tumor DNA Damage HEK293 Cells Histone-Lysine N-Methyltransferase Humans In Situ Hybridization, Fluorescence Kidney Neoplasms Neoplasm Proteins Neurofibromatosis 2 Polymorphism, Single Nucleotide Signal Transduction TOR Serine-Threonine Kinases Tumor Suppressor Proteins Ubiquitin Thiolesterase |
Issue Date: | 2016 | Publisher: | Nature Publishing Group | Citation: | 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 (2016). Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets. Nature Communications 7 : 13131. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms13131 | Rights: | Attribution 4.0 International | 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. | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/179799 | ISSN: | 2041-1723 | DOI: | 10.1038/ncomms13131 | Rights: | Attribution 4.0 International |
| Appears in Collections: | Elements Staff Publications |
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