Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1785033869187088384 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10143507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhangjun familialccmgenesmightnotbemaindriversforpathogenesisofsporadicccmsgeneticsimilaritybetweencancersandvascularmalformations AT croftjacob familialccmgenesmightnotbemaindriversforpathogenesisofsporadicccmsgeneticsimilaritybetweencancersandvascularmalformations AT lealexander familialccmgenesmightnotbemaindriversforpathogenesisofsporadicccmsgeneticsimilaritybetweencancersandvascularmalformations |