Molecular characterization of sarcomatoid clear cell renal cell carcinoma unveils new candidate oncogenic drivers. Academic Article uri icon

Overview

abstract

  • Sarcomatoid clear-cell renal cell carcinomas (sRCC) are associated with dismal prognosis. Genomic alterations associated with sarcomatoid dedifferentiation are poorly characterized. We sought to define the genomic landscape of sRCC and uncover potentially actionable therapeutic targets. We assessed the genomic landscape of sRCC using targeted panel sequencing including patients with microdissected sarcomatoid and epithelial components. Along with common genomic alterations associated with clear-cell histology, we found that Hippo was one of the most frequently altered pathways in these tumours. Hippo alterations were differentially enriched in sRCC compared to non-sRCC. Functional analysis showed that Hippo members mutations were associated with higher nuclear accumulation of YAP/TAZ, core effectors of the Hippo pathway. In a NF2-mutant sRCC model, YAP1 knockdown and NF2 reconstitution suppressed cell proliferation, tumour growth and invasion, both in vitro and in vivo. Overall, we show that Hippo pathway alterations are a feature of sRCC, and enable the exploration of the Hippo pathway as a novel potential therapeutic target.

publication date

  • January 20, 2020

Research

keywords

  • Carcinoma, Renal Cell
  • Gene Regulatory Networks
  • Kidney Neoplasms
  • Mutation

Identity

PubMed Central ID

  • PMC6971072

Scopus Document Identifier

  • 85078285774

Digital Object Identifier (DOI)

  • 10.1016/j.euf.2016.08.005

PubMed ID

  • 31959902

Additional Document Info

volume

  • 10

issue

  • 1