Somatic <i>PIK3CA</i> Mutations in Sporadic Cerebral Cavernous Malformations
Matthieu Peyre, Danielle Miyagishima, Franck Bielle, Françoise Chapon, Michael C. Sierant, Quitterie Venot, Julie Lerond, Pauline Marijon, Samiya Abi-Jaoude, Tuan Le Van, Karim Labrèche, Richard S. Houlston, Maxime Faisant, Stéphane Clémenceau, Anne‐Laure Boch, Aurélien Nouet, Alexandre Carpentier, Julien Boetto, Angeliki Louvi, Michel Kalamarides
Abstract
BACKGROUND: ), the genetic cause of sporadic CCMs, representing 80% of cases, remains incompletely understood. METHODS: We developed two mouse models harboring mutations identified in human meningiomas with the use of the prostaglandin D2 synthase (PGDS) promoter. We performed targeted DNA sequencing of surgically resected CCMs from patients and confirmed our findings by droplet digital polymerase-chain-reaction analysis. RESULTS: in mice and identified the PGDS-expressing pericyte as the probable cell of origin. CONCLUSIONS: were represented to a greater extent than mutations in any other gene. The contribution of somatic mutations in the genes that cause familial CCMs was comparatively small. (Funded by the Fondation ARC pour la Recherche contre le Cancer and others.).