title: Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation.
abstract: BACKGROUND
  An inherited germline P53 mutation has been identified in cases of childhood adrenocortical carcinoma (ACT), a neoplasm with a high incidence in southern Brazil. The penetrance of ACT in carriers of the point mutation, which encodes an arginine-to-histidine substitution at codon 337 of TP53 (R337H), has not been determined.
  
  
  OBJECTIVE
  To investigate the penetrance of childhood ACT in carriers of the R337H TP53 mutation.
  
  
  METHODS
  The family histories of 30 kindreds of 41 southern Brazilian children with ACT were obtained. A PCR based assay was used to detect this P53 mutation in a large number of relatives of children with ACT. In all, 927 individuals were tested for the mutation, 232 from the non-carrier and 695 (including the 40 probands) from the carrier parental lines.
  
  
  RESULTS
  40 children with ACT carried the TP53 R337H mutation; the remaining child with ACT was not tested. There was no evidence of Li-Fraumeni syndrome in any of the kindreds; however, seven met the criteria for Li-Fraumeni-like syndrome. The carrier parental line was identified in each kindred. Of the 695 individuals tested in the carrier parental line, 240 (34.5%) were positive for the mutation, while none of the 232 individuals in the other parental line carried the mutation. The penetrance of ACT was 9.9% (95% confidence interval, 8.7% to 11.1%).
  
  
  CONCLUSIONS
  The TP53 R337H mutation dramatically increases predisposition to childhood ACT but not to other cancers, and explains the increased frequency of ACT observed in this geographic region.
authors: B C
authors: BC
authors: Figueiredo
authors: R
authors: R
authors: Sandrini
authors: G P
authors: GP
authors: Zambetti
authors: R M
authors: RM
authors: Pereira
authors: C
authors: C
authors: Cheng
authors: W
authors: W
authors: Liu
authors: L
authors: L
authors: Lacerda
authors: M A
authors: MA
authors: Pianovski
authors: E
authors: E
authors: Michalkiewicz
authors: J
authors: J
authors: Jenkins
authors: C
authors: C
authors: Rodriguez-Galindo
authors: M J
authors: MJ
authors: Mastellaro
authors: S
authors: S
authors: Vianna
authors: F
authors: F
authors: Watanabe
authors: F
authors: F
authors: Sandrini
authors: S B I
authors: SB
authors: Arram
authors: P
authors: P
authors: Boffetta
authors: R C
authors: RC
authors: Ribeiro
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D017677:Age Distribution; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D019683:Penetrance; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53