EPAS1 and neoplasm: Transcriptomic studies further confirmed this initial observation by demonstrating that unsupervised classification of PPGL tumours allowed separating them into two major clusters of expression: cluster 1, characterized by a hypoxic signature, which comprised all TCA cycle mutations (cluster 1A) on one side and VHL and HIF2A mutated tumours (cluster 1B) on the other side, and cluster 2, regrouping RET, NF1, MAX, and TMEM127 related tumours, as well as most of the sporadic cases [47,48].