{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:03:51Z","timestamp":1790323431184,"version":"4.1.0"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"JSPS KAKENHI","award":["JP25K02899"],"award-info":[{"award-number":["JP25K02899"]}]},{"name":"JSPS KAKENHI","award":["JP23H03759"],"award-info":[{"award-number":["JP23H03759"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Somatic mutations affecting endothelial signaling pathways have emerged as important contributors to brain arteriovenous malformations (bAVMs). Although activating mutations in the RAS\/MAPK pathway have been frequently reported, alternative molecular mechanisms remain incompletely understood. We describe 2 autopsy-confirmed bAVMs harboring somatic PIK3CA mutations, including one case with a concurrent PTEN alteration. Histologically, both lesions demonstrated typical bAVM architecture without unusual structural features. Immunohistochemical analysis revealed lesion-restricted activation of the PI3K\/AKT\/mTOR pathway in endothelial cells; adjacent normal vessels were negative. In contrast, ERK phosphorylation was focal and limited; targeted sequencing did not identify pathogenic RAS\/MAPK mutations. These findings suggest dominant PI3K pathway activation with secondary or limited MAPK engagement. Variant allele frequencies were interpreted cautiously owing to whole-genome amplification from autopsy-derived tissue. In one case, prior Gamma Knife radiosurgery was considered to have contributed to the findings but histological features of radiation-associated vascular injury were not observed. Together, these findings support molecular heterogeneity in bAVMs and suggest that PIK3CA-driven PI3K pathway activation may contribute to vascular remodeling in RAS-negative lesions. Correlation of molecular alterations with pathway-specific endothelial activation highlights the value of integrated genetic and pathological assessment in bAVMs.<\/jats:p>","DOI":"10.1093\/jnen\/nlag054","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T11:45:01Z","timestamp":1778240701000},"page":"1117-1123","source":"Crossref","is-referenced-by-count":0,"title":["Somatic\n                    <i>PIK3CA<\/i>\n                    and\n                    <i>PTEN<\/i>\n                    mutations with endothelial PI3K\/AKT\/mTOR activation in RAS-negative brain arteriovenous malformations"],"prefix":"10.1093","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6441-3002","authenticated-orcid":false,"given":"Yukiko","family":"Hata","sequence":"first","affiliation":[{"name":"Department of Legal Medicine, Faculty of Medicine, University of Toyama , Toyama,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Neurology, Toyama University Hospital , Toyama,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shojiro","family":"Ichimata","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Faculty of Medicine, University of Toyama , Toyama,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kuroda","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, University of Toyama , Toyama,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6921-1768","authenticated-orcid":false,"given":"Naoki","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Faculty of Medicine, 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