Smoothened (SMO) [Neurosurgery Wiki]

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=====Smoothened (SMO)=====
In the absence of Hh, a cell-surface transmembrane protein called [[Patched]] (PTCH) acts to prevent high expression and activity of a 7 membrane spanning receptor called Smoothened (SMO).

{{ ::signaling_pathway.jpg|}}

A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. These results begin to define the spectrum of genetic alterations in meningiomas and identify potential therapeutic targets
((Brastianos PK, Horowitz PM, Santagata S, Jones RT, McKenna A, Getz G, Ligon
KL, Palescandolo E, Van Hummelen P, Ducar MD, Raza A, Sunkavalli A, Macconaill
LE, Stemmer-Rachamimov AO, Louis DN, Hahn WC, Dunn IF, Beroukhim R. Genomic
sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet.
2013 Mar;45(3):285-9. doi: 10.1038/ng.2526. PubMed PMID: 23334667; PubMed Central
PMCID: PMC3739288.
)).
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Identification of SMO and AKT1 mutations in meningiomas has raised the hope for targeted therapies. It would be useful to know the precise frequency of these mutations in anatomical subgroups and clarify their prognostic value.

Molecular diagnosis of SMO L412F/W535L and AKT1 E17K mutations improves prognostic evaluation in [[olfactory groove meningioma]]s and opens new therapeutic perspectives with SMO or AKT inhibitors for recurrent cases
((Boetto J, Bielle F, Sanson M, Peyre M, Kalamarides M. SMO mutation status
defines a distinct and frequent molecular subgroup in olfactory groove
meningiomas. Neuro Oncol. 2017 Jan 12. pii: now276. doi: 10.1093/neuonc/now276.
[Epub ahead of print] PubMed PMID: 28082415.
)).