title: Somatic mutations rather than viral infection classify focal cortical dysplasia type II as mTORopathy.
abstract: Genetic studies in focal cortical dysplasia type II (FCD II) provided ample evidence for somatic mutations in genes associated with the mammalian target of rapamycin (mTOR) pathway. Interestingly, the mTOR pathway can also be activated by the E6 oncogene of human papilloma viruses, and available data in FCD II remain controversial. We review and discuss the contradicting etiologies.
  
  
  
  The neuroembryologic basis of cortical development and timing of a somatic mutation occurring in proliferating neuroblasts can mechanistically link mTORopathies. When a somatic mutation occurs in proliferating neuroblasts at an early stage of their anticipated total number of 33 mitotic cell cycles, large hemispheric lesions will develop from their affected progeny. Somatic mutations occurring at later periods of neuroblast expansion will result in circumscribed and small FCD II. Recently published data did not support evidence for viral infection in FCD II.
  
  
  
  Genetic and histopathological data rather than viral infection classify FCD II into the spectrum of mTORopathies. Size and extent of the resulting cerebral lesion can be well explained by timing of somatic mutations during cortical development.
authors: aDepartment of Neuropathology, University Hospital Erlangen, Erlangen, Germany bEpilepsy Center, Cleveland Clinic Foundation, Cleveland, Ohio, USA cDepartment of Paediatrics dDepartment of Pathology (Neuropathology) eDepartment of Clinical Neurosciences, University of Calgary Faculty of Medicine, Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.
authors: Ingmar
authors: I
authors: Blümcke
authors: Harvey B
authors: HB
authors: Sarnat
mesh_terms: D049109:Cell Proliferation; D004827:Epilepsy / Q000235:genetics* / Q000821:virology; D006801:Humans; D065703:Malformations of Cortical Development, Group I / Q000235:genetics* / Q000821:virology; D009154:Mutation; D030361:Papillomavirus Infections / Q000150:complications*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases