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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MSK Authors
  1. Paul Russo
    499 Russo
  2. Robert Motzer
    923 Motzer
  3. Satish K Tickoo
    398 Tickoo
  4. Martin Henner Voss
    169 Voss
  5. Yingbei Chen
    279 Chen
  6. Lu Wang
    146 Wang
  7. Yiyu Dong
    21 Dong
  8. James J Hsieh
    121 Hsieh
  9. Achim Jungbluth
    385 Jungbluth
  10. Emily H Cheng
    61 Cheng
  11. Michael Forman Berger
    497 Berger
  12. Victor Reuter
    1070 Reuter
  13. Wei Li
    6 Li
  14. Nikolaus D Schultz
    263 Schultz
  15. Helen Hyeong-Eun Won
    90 Won
  16. Angela Rose Brannon
    34 Brannon
  17. William Lee
    38 Lee
  18. Abraham Ari Hakimi
    185 Hakimi
  19. Jianing Xu
    11 Xu
  20. Patricia Ibai Wang
    12 Wang