title: Clinicopathologic comparison of familial versus sporadic atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system.
abstract: BACKGROUND
  Central nervous system (CNS) atypical teratoid/rhabdoid tumors (AT/RT) are aggressive tumors usually diagnosed in young children and characterized by SMARCB1 (INI1, hSNF5) gene abnormalities. Despite initial chemo-radiation responsiveness, most children die of progressive disease (PD). Little data regarding familial AT/RT clinical course exist. This study described and compared familial (F) versus sporadic (S) AT/RT and elucidated SMARCB1 mutations and inheritance patterns.
  
  
  METHODS
  A retrospective chart review, pedigree, and SMARCB1 analysis were done.
  
  
  RESULTS
  Between January 1989 and June 2009, 20 children with CNS AT/RT were diagnosed, 8-S and 12-F. Median age at diagnosis (months) of S and F patient were: 13 and 4.8, respectively. Median survival (months) was S-21, F4.5, and 8-all. Pedigree analyses showed unaffected parent carriers with multiple affected offspring.
  
  
  CONCLUSIONS
  Children with F-AT/RT are younger, have more extensive disease, and are more likely to die from PD than children with S-AT/RT. Surgery, radiation, and chemotherapy were important in achieving long-term survival. Pedigree analysis supports autosomal dominant inheritance pattern with incomplete penetrance. Germline SMARCB1 mutation analysis is important in all patients diagnosed with AT/RT to (1) determine actual incidence of F-AT/RT, (2) determine penetrance of predisposing mutations, (3) provide appropriate genetic counseling, and (4) establish surveillance screening guidelines.
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, Utah, USA. carol.bruggers@imail.org
authors.forename: Carol S
authors.initials: CS
authors.lastname: Bruggers
authors.forename: Steven B
authors.initials: SB
authors.lastname: Bleyl
authors.forename: Theodore
authors.initials: T
authors.lastname: Pysher
authors.forename: Philip
authors.initials: P
authors.lastname: Barnette
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Afify
authors.forename: Marion
authors.initials: M
authors.lastname: Walker
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Biegel
mesh_terms: D016543:Central Nervous System Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D012189:Retrospective Studies; D018335:Rhabdoid Tumor / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D000071796:SMARCB1 Protein; D015996:Survival Rate; D013724:Teratoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D014157:Transcription Factors / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors