title: SMARCB1 deficiency in tumors from the peripheral nervous system: a link between schwannomas and rhabdoid tumors?
abstract: BACKGROUND
  Inactivation of SMARCB1 tumor-suppressor gene was originally described as highly specific for rhabdoid tumors (RTs). Nevertheless, recent reports have illustrated that SMARCB1 alterations also characterize other tumors; in particular, some familial schwannomatosis and epithelioid malignant peripheral nerve sheath tumors, both from peripheral nervous system (PNS) origin, lack BAF47 expression. To document the putative role of SMARCB1 in PNS, we reviewed PNS tumors referred to our institution for a molecular analysis of SMARCB1 because of histologic features compatible with RT.
  
  
  METHODS
  Clinicopathologic, radiologic, and molecular characteristics were detailed for the 12 cases showing loss of expression and/or biallelic inactivation of SMARCB1. The status of the NF2 gene, likely to synergize with SMARCB1 in PNS tumors, was also analyzed.
  
  
  RESULTS
  Patients' age ranged from 0 to 45 years (median age, 6.6 y). Neurological symptoms were observed in 7/12 cases with radiologic features evoking a neuroblastic tumor in 6 cases and a peripheral nerve tumor in 4 cases. The mean delay before diagnosis was 3 months. Histologic examination revealed rhabdoid features in 11/12 tumors. All tumors showed a complete loss of SMARCB1 expression. Interestingly, adjacent nervous proliferation resembling neurofibromas were observed in 3 cases, suggesting a multistep transformation. Three tumors harbored a hemizygous deletion at the NF2 locus, but all NF2 sequences were normal.
  
  
  CONCLUSIONS
  We report the first series of PNS RT. In patients with aggressive PNS tumors, RT should be suspected, and anti-SMARCB1 immunohistochemical analysis should be performed. SMARCB1 inactivation, occasionally associated with NF2 deletion, might have oncogenic effects in peripheral nerves.
authors.affiliation: Department of Pediatric Oncology, Catholic University, A. Gemelli Hospital, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rizzo
authors.forename: Paul
authors.initials: P
authors.lastname: Fréneaux
authors.forename: Hervé
authors.initials: H
authors.lastname: Brisse
authors.forename: Camille
authors.initials: C
authors.lastname: Louvrier
authors.forename: Delphine
authors.initials: D
authors.lastname: Lequin
authors.forename: André
authors.initials: A
authors.lastname: Nicolas
authors.forename: Dominique
authors.initials: D
authors.lastname: Ranchère
authors.forename: Virginie
authors.initials: V
authors.lastname: Verkarre
authors.forename: Anne
authors.initials: A
authors.lastname: Jouvet
authors.forename: Christelle
authors.initials: C
authors.lastname: Dufour
authors.forename: Christine
authors.initials: C
authors.lastname: Edan
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Stéphan
authors.forename: Daniel
authors.initials: D
authors.lastname: Orbach
authors.forename: Sabine
authors.initials: S
authors.lastname: Sarnacki
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pierron
authors.forename: Béatrice
authors.initials: B
authors.lastname: Parfait
authors.forename: Michel
authors.initials: M
authors.lastname: Peuchmaur
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdeaut
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020868:Gene Silencing; D016515:Genes, Neurofibromatosis 2; D020022:Genetic Predisposition to Disease; D057898:Hemizygote; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009442:Neurilemmoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D010297:Paris; D010524:Peripheral Nervous System Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests; D018335:Rhabdoid Tumor / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D000071796:SMARCB1 Protein; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors