title: SMO mutation status defines a distinct and frequent molecular subgroup in olfactory groove meningiomas.
abstract: Meningiomas are the most common primary intracranial tumors in adults. 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.
  
  
  
  We used the Sanger sequencing technique to characterize 79 samples of olfactory groove meningiomas for SMO (L412F and W535L) and AKT1E17K mutations. We reviewed clinical data to assess the prognostic value of these mutations in this anatomical subgroup.
  
  
  
  Out of the 79 patients with olfactory groove meningiomas, we identified targetable mutations in 34 patients (43%) (22 patients [28%] with SMO mutation-L412F almost exclusively-and 12 patients [15%] with AKT1 mutation). Meningiomas in the SMO-mutant group had an overall 36% recurrence rate, significantly higher than in the AKT1-mutant group (16%) and in the "SMO and AKT1 wildtype" group (11%) (χ2 test, P = .04). All late recurrences (after 5 y) occurred in the SMO-mutant group. Among grade I meningiomas, the SMO-mutant group was identified as having a significantly poorer prognosis. World Health Organization histological grade II (P = .006) and incomplete resection (P = .001) were independently associated with shorter recurrence-free survival.
  
  
  
  Molecular diagnosis of SMOL412F/W535L and AKT1E17K mutations improves prognostic evaluation in olfactory groove meningiomas and opens new therapeutic perspectives with SMO or AKT inhibitors for recurrent cases.
authors.affiliation: Department of Neurosurgery, Gui de Chauliac Hospital, Montpellier University Medical Center, Montpellier, France.|INSERM U1127, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Boetto
authors.affiliation: INSERM U1127, Paris, France.|Department of Neuropathology, APHP, Hôpital de La Pitié-Salpêtrière, Paris, France.|Sorbonne Universités, UPMC, Paris, France.|OncoNeuroTek, Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bielle
authors.affiliation: INSERM U1127, Paris, France.|Sorbonne Universités, UPMC, Paris, France.|Department of Neurology, APHP, Hôpital de La Pitié-Salpêtrière, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.affiliation: INSERM U1127, Paris, France.|Sorbonne Universités, UPMC, Paris, France.|Department of Neurosurgery, APHP, Hôpital de La Pitié-Salpêtrière, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Peyre
authors.affiliation: INSERM U1127, Paris, France.|Sorbonne Universités, UPMC, Paris, France.|Department of Neurosurgery, APHP, Hôpital de La Pitié-Salpêtrière, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Kalamarides
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000145:classification* / Q000235:genetics / Q000473:pathology; D008579:Meningioma / Q000145:classification* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D000072086:Smoothened Receptor / Q000235:genetics*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C491023:SMO protein, human; D000072086:Smoothened Receptor; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; SMO; meningioma; molecular pathology; olfactory groove meningioma