Sequential events of VeMs-derived CCM lesions in sporadic CCM cases. Like tumorigenic events observed in breast cancer, somatic point mutations in angiogenic factors such as TIE2, AKT1, MAP3K3, and PIK3CA, involved in PI3K signaling, have been identified as a cause of enhanced RTK/PI3K/AKT/mTOR signaling in ECs and play a key role in the pathogenesis of VeMs. Here, MAP3K3 is linked to cerebral cavernous malformation.