These GOF mutations, which have also been considered powerful modifiers of CCM pathogenesis (see Section 3.4, below), drive excessive, abnormal vascular proliferation, suggesting that PI3K pathway activation contributes to the acquisition of clonal growth competence within CCM lesions, regardless of whether the initiating event is familial (germline) or sporadic. This evidence concerns the gene PIK3CA and cerebral cavernous malformation.