MAP3K3 and cerebral cavernous malformation: However, very recent studies, specifically those performed by distinct research groups on surgical samples of human CCM lesions, have led to the breakthrough discovery that somatic mutations in the three known CCM genes are rarely present in sporadic CCMs, which are instead most frequently associated with somatic mutations in genes implicated in the PI3K/Akt and MAPK pathways, including PIK3CA and MAP3K3 [14,15,16].