title: Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers.
abstract: BACKGROUND
  Rhabdomyosarcoma (RMS) represents a diverse category of myogenic malignancies with marked differences in molecular alterations and histology. This study examines the question if RMS predisposition due to germline TP53 mutations correlates with certain RMS histologies.
  
  
  METHODS
  The histology of RMS tumors diagnosed in 8 consecutive children with TP53 germline mutations was reviewed retrospectively. In addition, germline TP53 mutation analysis was performed in 7 children with anaplastic RMS (anRMS) and previously unknown TP53 status.
  
  
  RESULTS
  RMS tumors diagnosed in 11 TP53 germline mutation carriers all exhibited nonalveolar, anaplastic histology as evidenced by the presence of enlarged hyperchromatic nuclei with or without atypical mitotic figures. Anaplastic RMS was the first malignant diagnosis for all TP53 germline mutation carriers in this cohort, and median age at diagnosis was 40 months (mean, 40 months ± 15 months; range, 19-67 months). The overall frequency of TP53 germline mutations was 73% (11 of 15 children) in pediatric patients with anRMS. The frequency of TP53 germline mutations in children with anRMS was 100% (5 of 5 children) for those with a family cancer history consistent with Li-Fraumeni syndrome (LFS), and 80% (4 of 5 children) for those without an LFS cancer phenotype.
  
  
  CONCLUSIONS
  Individuals harboring germline TP53 mutations are predisposed to develop anRMS at a young age. If future studies in larger anRMS cohorts confirm the findings of this study, the current Chompret criteria for LFS should be extended to include children with anRMS irrespective of family history.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Pediatric Hematology/ Oncology, Boston Children's Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; Howard Hughes Medical Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, Massachusetts; Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Simone
authors.initials: S
authors.lastname: Hettmer
authors.forename: Natasha M
authors.initials: NM
authors.lastname: Archer
authors.forename: Gino R
authors.initials: GR
authors.lastname: Somers
authors.forename: Ana
authors.initials: A
authors.lastname: Novokmet
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Wagers
authors.forename: Lisa
authors.initials: L
authors.lastname: Diller
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez-Galindo
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Teot
authors.forename: David
authors.initials: D
authors.lastname: Malkin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
keywords: Li-Fraumeni syndrome; TP53; anaplasia; germline mutations; rhabdomyosarcoma