Zhang Jun, Croft Jacob, Le Alexander
Departments of Molecular & Translational Medicine (MTM), Texas Tech University Health Science Center El Paso (TTUHSCEP), El Paso, TX 79905, USA.
J Pers Med. 2023 Apr 17;13(4):673. doi: 10.3390/jpm13040673.
Cerebral cavernous malformations (CCMs) are abnormally dilated intracranial capillaries that form cerebrovascular lesions with a high risk of hemorrhagic stroke. Recently, several somatic "activating" gain-of-function (GOF) point mutations in PIK3CA (phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit p110α) were discovered as a dominant mutation in the lesions of sporadic forms of cerebral cavernous malformation (sCCM), raising the possibility that CCMs, like other types of vascular malformations, fall in the PIK3CA-related overgrowth spectrum (PROS). However, this possibility has been challenged with different interpretations. In this review, we will continue our efforts to expound the phenomenon of the coexistence of gain-of-function (GOF) point mutations in the gene and loss-of-function (LOF) mutations in genes in the CCM lesions of sCCM and try to delineate the relationship between mutagenic events with CCM lesions in a temporospatial manner. Since GOF PIK3CA point mutations have been well studied in reproductive cancers, especially breast cancer as a driver oncogene, we will perform a comparative meta-analysis for GOF PIK3CA point mutations in an attempt to demonstrate the genetic similarities shared by both cancers and vascular anomalies.
脑海绵状血管畸形（CCMs）是异常扩张的颅内毛细血管，它们形成具有出血性中风高风险的脑血管病变。最近，在散发性脑海绵状血管畸形（sCCM）病变中发现了PIK3CA（磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基p110α）中的几种体细胞“激活”功能获得性（GOF）点突变，作为主要突变，这增加了CCMs与其他类型血管畸形一样属于PIK3CA相关过度生长谱系（PROS）的可能性。然而，这种可能性受到了不同解释的挑战。在本综述中，我们将继续努力阐述sCCM的CCM病变中PIK3CA基因功能获得性（GOF）点突变与其他基因功能丧失性（LOF）突变共存的现象，并试图以时空方式描绘诱变事件与CCM病变之间的关系。由于GOF PIK3CA点突变在生殖系统癌症，特别是作为驱动癌基因的乳腺癌中已得到充分研究，我们将对GOF PIK3CA点突变进行比较荟萃分析，以试图证明这两种癌症与血管异常之间共有的遗传相似性。
