VHL and neoplasm: Nevertheless, gene expression studies have suggested that most PCCs and PGLs can be classified into two distinct groups (cluster 1 and cluster 2) by transcription profiling: cluster 1 includes tumours that harbour mutations in genes linked to the hypoxic gene response (VHL, HIF2A, SDHA, SDHB, SDHC, and SDHD) and cluster 2 contains tumours harbouring mutations in genes that are involved in the kinase signalling characterized by the activation of the PIK3/AKT/mTOR and RAS/RAF/ERK pathways (RET, NF1, TMEM127, MAX, and HRAS) [14–18].