title: Predisposition to atypical teratoid/rhabdoid tumor due to an inherited INI1 mutation.
abstract: BACKGROUND
  Germline mutations of the INI1 gene predispose children to the development of rhabdoid tumors. Reports of familial cases, however, are extremely rare.
  
  
  METHODS
  We have identified a three-generation family in which two half-brothers were diagnosed with central nervous system atypical teratoid/rhabdoid tumors (AT/RT). The two boys, diagnosed at 2 months and 17 months of age, had a germline insertion mutation in exon 4 of the INI1 gene that was inherited from their healthy mother. A maternal uncle died in childhood from a brain tumor and a malignant rhabdoid tumor of the kidney, and presumably carried the same germline mutation. As the mother and uncle had different fathers, the grandmother is also an obligate carrier of the mutation.
  
  
  CONCLUSIONS
  The identification of two unaffected carriers in a family segregating a germline mutation and rhabdoid tumor supports the hypothesis that there may be variable risks of development of rhabdoid tumor in the context of a germline mutation. There may be a developmental window in which most rhabdoid tumors occur. This family highlights the importance of mutation analysis in all patients with a suspected rhabdoid tumor.
authors.affiliation: Department of Radiation Oncology, Tulane University, New Orleans, Los Angeles, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Janson
authors.forename: Lucien A
authors.initials: LA
authors.lastname: Nedzi
authors.forename: Odile
authors.initials: O
authors.lastname: David
authors.forename: Marshall
authors.initials: M
authors.lastname: Schorin
authors.forename: John W
authors.initials: JW
authors.lastname: Walsh
authors.forename: Meena
authors.initials: M
authors.lastname: Bhattacharjee
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pridjian
authors.forename: Lu
authors.initials: L
authors.lastname: Tan
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Judkins
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Biegel
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree; D018335:Rhabdoid Tumor / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D000071796:SMARCB1 Protein; D012680:Sensitivity and Specificity; D013724:Teratoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; 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