表型
PI3K/AKT/mTOR通路
发病机制
体细胞
突变体
生物
P110α
神经科学
调节器
功能(生物学)
突变
遗传学
癌症研究
生物信息学
信号转导
基因
免疫学
作者
Jun Zhang,Johnathan Abou‐Fadel,Mellisa Renteria,Ofek Belkin,Bixia Chen,Yuan Zhu,Philipp Dammann,Daniele Rigamonti
标识
DOI:10.1136/jnnp-2022-328901
摘要
Somatic gain-of-function (GOF) mutations in phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), the catalytic subunit of phosphoinositide 3-kinase (PI3K), have been recently discovered in cerebral cavernous malformations (CCMs), raising the possibility that the activation of PI3K pathways is a possible universal regulator of vascular morphogenesis. However, there have been contradicting data presented among various groups and studies. To enhance the current understanding of vascular anomalies, it is essential to explore this possible relationship between altered PI3K signalling pathways and its influence on the pathogenesis of CCMs. GOF PIK3CA -mutants have been linked to overgrowth syndromes, allowing this group of disorders, resulting from somatic activating mutations in PIK3CA, to be collectively named as PIK3CA -related overgrowth spectrum disorders. This paper reviews and attempts to conceptualise the relationships and differences among clinical presentations, genotypic and phenotypic correlations and possible coexistence of PIK3CA and CCM mutations/phenotypes in CCM lesions. Finally, we present a model reflecting our hypothetical understanding of CCM pathogenesis based on a systematic review and conceptualisation of data obtained from other studies.
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