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Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations

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 c...

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Autores principales: Zhang, Jun, Croft, Jacob, Le, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143507/
https://www.ncbi.nlm.nih.gov/pubmed/37109059
http://dx.doi.org/10.3390/jpm13040673
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author Zhang, Jun
Croft, Jacob
Le, Alexander
author_facet Zhang, Jun
Croft, Jacob
Le, Alexander
author_sort Zhang, Jun
collection PubMed
description 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 PIK3CA gene and loss-of-function (LOF) mutations in CCM 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.
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spelling pubmed-101435072023-04-29 Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations Zhang, Jun Croft, Jacob Le, Alexander J Pers Med Review 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 PIK3CA gene and loss-of-function (LOF) mutations in CCM 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. MDPI 2023-04-17 /pmc/articles/PMC10143507/ /pubmed/37109059 http://dx.doi.org/10.3390/jpm13040673 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Zhang, Jun
Croft, Jacob
Le, Alexander
Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations
title Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations
title_full Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations
title_fullStr Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations
title_full_unstemmed Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations
title_short Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations
title_sort familial ccm genes might not be main drivers for pathogenesis of sporadic ccms-genetic similarity between cancers and vascular malformations
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143507/
https://www.ncbi.nlm.nih.gov/pubmed/37109059
http://dx.doi.org/10.3390/jpm13040673
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