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Genomic analysis of 161 papillary kidney cancers showed that type 1 tumours are driven by MET alterations while type 2 tumours are a mixture of distinct diseases including CDKN2A-silenced, SETD2-mutated, fumarate hydratase-deficient and a CpG island methylator phenotype with very short survival.
Integrated genomic study by The Cancer Genome Atlas of 161 papillary renal cell carcinomas showing MET alterations in 81 percent of type 1 tumours, and in type 2 tumours CDKN2A loss, SETD2 and other chromatin modifier mutations, TFE3 fusions, NRF2-ARE pathway activation and a CpG island methylator phenotype associated with fumarate hydratase deficiency and the worst outcomes.
Papillary renal cell carcinoma is several diseases; the finding of MET dependence in type 1 tumours underpins the use of cabozantinib and savolitinib, and the 2022 WHO classification dropped the type 1 and 2 split in favour of molecular entities.