title: Non-linkage of familial rhabdoid tumors to SMARCB1 implies a second locus for the rhabdoid tumor predisposition syndrome.
abstract: BACKGROUND
  Rhabdoid tumors represent an independent entity among embryonal neoplasms. These tumors affect the kidney (RTK, rhabdoid tumor of kidney) and central nervous system (AT/RT, atypical teratoid, rhabdoid tumor), but may also be found in peripheral soft tissue. Unifying features include immunohistochemical characteristics and inactivation of the putative tumor suppressor gene SMARCB1 (hSNF5/INI1) in chromosome 22q11.2. Several familial cases have been published and summarized under the term rhabdoid tumor predisposition syndrome. In all of the published familial cases, inactivation of SMARCB1 was detected in tumor tissues.
  
  
  RESULTS
  We report on a family with three children, two of which were affected by rhabdoid tumors, one RTK, the other an AT/RT. While both children demonstrated typical morphological and clinical features neither the RTK nor the AT/RT showed evidence for inactivation of SMARCB1 in molecular studies including CGH and array CGH, FISH, gene dosage analysis by dHPLC, and DNA-sequencing. Immunohistochemistry for SMARCB1 showed normal expression within the nuclei of tumor cells. Furthermore, both children inherited different paternal and maternal SMARCB1 alleles evidenced by haplotype analysis. Conventional cytogenetic, FISH, and mutation analyses lacked evidence for SMARCB1 aberrations or gross chromosomal changes in the parents.
  
  
  CONCLUSIONS
  We thus demonstrate a family with rhabdoid tumor predisposition syndrome without linkage to SMARCB1. This finding indicates that other loci than SMARCB1 below the resolution of array CGH are involved in the origin of these tumors. Our data impact on the clinical counseling of affected families and warrant further studies in the molecular biology of these enigmatic tumors.
authors.affiliation: University Children's Hospital Muenster, Department of Paediatric Haematology and Oncology, Muenster, Germany. fruhwald@uni-muenster.de
authors.forename: Michael C
authors.initials: MC
authors.lastname: Frühwald
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wirth
authors.forename: Gabriele
authors.initials: G
authors.lastname: Köhler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneppenheim
authors.forename: Jose Igancio Martin
authors.initials: JI
authors.lastname: Subero
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Uwe
authors.initials: U
authors.lastname: Kordes
authors.forename: Heribert
authors.initials: H
authors.lastname: Jürgens
authors.forename: Josef
authors.initials: J
authors.lastname: Vormoor
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics*; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods; D018335:Rhabdoid Tumor / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D000071796:SMARCB1 Protein; D012680:Sensitivity and Specificity; D013577:Syndrome; D014057:Tomography, X-Ray Computed / Q000379:methods; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors