PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism.

ABSTRACT: Vascular malformations are thought to be monogenic disorders that result in dysregulated growth of blood vessels. In the brain, cerebral cavernous malformations (CCMs) arise owing to inactivation of the endothelial CCM protein complex, which is required to dampen the activity of the kinase MEKK3^1-4. Environmental factors can explain differences in the natural history of CCMs between individuals⁵, but why single CCMs often exhibit sudden, rapid growth, culminating in strokes or seizures, is unknown. Here we show that growth of CCMs requires increased signalling through the phosphatidylinositol-3-kinase (PI3K)-mTOR pathway as well as loss of function of the CCM complex. We identify somatic gain-of-function mutations in PIK3CA and loss-of-function mutations in the CCM co

SUBMITTER: Ren AA 

PROVIDER: S-EPMC8626098 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature