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Updated: Aug 6, 2026
06:51
A Patient-Derived Xenograft Model for Venous Malformation
Published on: June 15, 2020
Somatic PIK3CA and PTEN mutations with endothelial PI3K/AKT/mTOR activation in RAS-negative brain arteriovenous
Yukiko Hata1, Ryo Tanaka2, Shojiro Ichimata1
1Department of Legal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan.
Journal of Neuropathology and Experimental Neurology
|July 25, 2026
Summary
Somatic PIK3CA mutations drive brain arteriovenous malformations (bAVMs) by activating the PI3K pathway, even in RAS/MAPK-negative cases. This highlights molecular diversity in bAVM development.
Area of Science:
- Vascular biology
- Molecular genetics
- Neuropathology
Background:
- Somatic mutations in endothelial signaling pathways are key drivers of brain arteriovenous malformations (bAVMs).
- While RAS/MAPK pathway mutations are common, other molecular mechanisms remain unclear.
Purpose of the Study:
- To investigate alternative molecular pathways involved in bAVM pathogenesis.
- To characterize the role of PIK3CA mutations in bAVMs.
Main Methods:
- Autopsy-confirmed bAVM samples were analyzed.
- Histological and immunohistochemical analyses were performed.
- Targeted sequencing and whole-genome amplification were utilized.
Main Results:
- Two bAVMs with somatic PIK3CA mutations were identified, one with a concurrent PTEN alteration.
- Lesion-restricted PI3K/AKT/mTOR pathway activation was observed in endothelial cells.
- RAS/MAPK pathway activation was limited, with no pathogenic RAS/MAPK mutations detected.
Conclusions:
- PIK3CA-driven PI3K pathway activation contributes to vascular remodeling in RAS-negative bAVMs.
- Findings suggest molecular heterogeneity in bAVM development.
- Integrated genetic and pathological assessment is valuable for understanding bAVMs.
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