charge_syndrome [Neurosurgery Wiki]

This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong.
[[Tumorigenic]] and non-neoplastic [[tissue]] [[injury]] occurs via the ischemic [[microenvironment]] defined by low [[oxygen]], [[pH]], and [[nutrient]]s due to [[blood]] supply malfunction. Ischemic conditions exist within regions of pseudopalisading [[necrosis]], a pathological hallmark of [[glioblastoma]] (GBM), the most common primary malignant brain tumor in adults. To recapitulate the physiologic microenvironment found in GBM tumors and tissue injury, Boyd et al., from [[Birmingham]] [[Alabama]] developed an in vitro ischemic model and identified chromodomain helicase DNA binding protein 7 (CHD7) as a novel ischemia-regulated gene. Point [[mutation]]s in the CHD7 gene are causal in [[CHARGE syndrome]], a CNS developmental disorder, and interrupt the epigenetic functions of CHD7 in regulating [[neural stem cell]] maintenance and development. Using this ischemic system, they observed microenvironment-mediated decreases in CHD7 expression in [[brain tumor]] initiating cells and neural stem cells. Validating the approach, CHD7 was suppressed in the perinecrotic niche of GBM patient and [[xenograft]] sections, and an interrogation of patient gene expression datasets determined correlations between low CHD7, increasing [[glioma grade]] and worse patient [[outcome]]s. Segregation of GBM by molecular subtype revealed a novel observation that CHD7 expression is elevated in [[proneural]] vs [[mesenchymal glioblastoma]]. Genetic targeting of CHD7 and subsequent gene [[ontology]] analysis of [[RNA sequencing]] data indicated [[angiogenesis]] as a primary biological function affected by CHD7 expression changes. They validated this finding in tube formation assays and [[vessel]] formation in [[orthotopic]] GBM models. Together, this data provide further understanding of [[molecular]] responses to ischemia and a novel function of CHD7 in regulating angiogenesis in both neoplastic and non-neoplastic systems. 

Inactivating [[mutation]]s in the epigenetic modifier chromodomain helicase DNA binding protein 7 (CHD7) are associated with [[CHARGE syndrome]], a disorder causing [[Coloboma]], Heart defects, Atresia choanae, growth Retardation, Genital abnormalities, and Ear abnormalities. 

They find for the first time that ischemic microenvironments repress CHD7 levels in neural progenitors and brain tumor initiating cells/cancer stem cells. This novel results also demonstrate that reduced levels of CHD7 in neural progenitors or brain tumor initiating cells increase angiogenesis. They believed that this data may have important implications for development, [[stem cell]]s, and [[cancer]]
((Boyd NH, Walker K, Ayokanmbi A, Gordon ER, Whetsel J, Smith CM, Sanchez RG,
Lubin F, Chakraborty A, Tran AN, Herting C, Hambardzumyan D, Yancey Gillespie G, 
Hackney JR, Cooper SJ, Jiao K, Hjelmeland AB. [[CHD7]] is Suppressed in the
Perinecrotic/Ischemic [[Microenvironment]] and is a Novel Regulator of [[Glioblastoma]]
[[Angiogenesis]]. Stem Cells. 2019 Jan 10. doi: 10.1002/stem.2969. [Epub ahead of
print] PubMed PMID: 30629778.
)).