Whole Exome Sequencing of Papillary Type 2 Renal Cell Carcinoma and matched normal kidney tissue reveals NRF2 activation
NRF2 activation in sporadic Papillary Type 2 Renal Cell Carcinoma can be a result of loss of function mutation to CUL3, dominant negative mutation to SIRT1, as well as, gain of function mutation to NRF2.  The expressions of these driver genes as well as NRF2 activation in the clinical samples were validated through transcriptome sequencing.  Knocking down endogenous expression of CUL3 or ectopic expression of mutant SIRT1 and NRF2 in primary kidney tubular epithelial cells activates NRF2, solidifying the role of those identified mutations in driving the primary biochemical phenotype of the PRCC2.