title: Frequent hSNF5/INI1 germline mutations in patients with rhabdoid tumor.
abstract: OBJECTIVE
  Germline hSNF5/INI1 mutations are responsible for hereditary cases of rhabdoid tumors (RT) that constitute the rhabdoid predisposition syndrome (RPS). Our study provides the first precise overview of the prevalence of RPS within a large cohort of RT.
  
  
  METHODS
  hSNF5/INI1 coding exons were investigated by sequencing and by multiplex ligation-dependent probe amplification.
  
  
  RESULTS
  Seventy-four constitutional DNAs from 115 apparently sporadic RT were analyzed from 1999 to 2009. Germline mutations were found in 26 patients (35%). Data from 9 individuals from 5 RPS families (siblings) were also studied. The median age at diagnosis was much lower (6 months) in patients with germline mutation (P < 0.01) than in patients without (18 months). Nevertheless, 7 of 35 patients with germline mutation (20%) developed the disease after 2 years of age. The mutation could be detected in only 1 parent whereas germline blood DNA was wild type in the 20 other parent pairs, therefore indicating the very high proportion of germ-cell mosaicism or of de novo mutations in RPS. The former hypothesis could be clearly documented in 1 case in which prenatal diagnosis was positive in a new pregnancy. Finally, the 2 years' overall survival was 7% in mutated and 29% in wild-type patients, mainly due to the worse outcome of RT in younger patients.
  
  
  CONCLUSIONS
  Our results show a high proportion of germline mutations in patients with RT that can be found at any age and up to 60% in the youngest patients. Genetic counseling is recommended given the low but actual risk of familial recurrence.
authors.affiliation: CHU Nantes, Service d'Hémato-Oncologie Pédiatrique, Nantes, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdeaut
authors.forename: Delphine
authors.initials: D
authors.lastname: Lequin
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugières
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Reynaud
authors.forename: Christelle
authors.initials: C
authors.lastname: Dufour
authors.forename: François
authors.initials: F
authors.lastname: Doz
authors.forename: Nicolas
authors.initials: N
authors.lastname: André
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Stephan
authors.forename: Yves
authors.initials: Y
authors.lastname: Pérel
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
authors.forename: Daniel
authors.initials: D
authors.lastname: Orbach
authors.forename: Christophe
authors.initials: C
authors.lastname: Bergeron
authors.forename: Xavier
authors.initials: X
authors.lastname: Rialland
authors.forename: Paul
authors.initials: P
authors.lastname: Fréneaux
authors.forename: Dominique
authors.initials: D
authors.lastname: Ranchere
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: Georges
authors.initials: G
authors.lastname: Audry
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Puget
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Joan Carles Ferreres
authors.initials: JC
authors.lastname: Pinas
authors.forename: Valeria
authors.initials: V
authors.lastname: Capra
authors.forename: Véronique
authors.initials: V
authors.lastname: Mosseri
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coupier
authors.forename: Marion
authors.initials: M
authors.lastname: Gauthier-Villars
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pierron
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
mesh_terms: D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D018335:Rhabdoid Tumor / Q000175:diagnosis / Q000235:genetics*; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors