title: Association of the highly prevalent TP53 R337H mutation with pediatric choroid plexus carcinoma and osteosarcoma in southeast Brazil.
abstract: BACKGROUND
  The inherited, low-penetrance arginine-to-histidine substitution at codon 337 (R337H) of the tumor protein 53 gene (TP53) is clustered in southeast Brazil (estimated frequency, 0.3%). Although its tumorigenic effect initially appeared to be tissue-specific, recent evidence suggests its association with a broader range of tumors. Therefore, the authors of this report investigated the spectrum of pediatric malignancies associated with the TP53 R337H mutation at a single referral institution in southeast Brazil.
  
  
  METHODS
  Genomic DNA samples from 493 children with malignancies were screened for the R337H mutation. Available tumor samples from carriers were investigated for loss of heterozygosity (LOH) and nuclear p53 accumulation. Clinical data were obtained from medical records.
  
  
  RESULTS
  Sixty-five of 70 patients (93%) with adrenocortical tumors (ACTs), 9 of 13 patients (69%) with choroid plexus carcinoma (CPC), and 3 of 41 patients (7.3%) with osteosarcoma carried the mutation. The proportion of CPC to choroid plexus papilloma (CPP) was much higher than that reported elsewhere. Osteosarcoma in carriers had a significantly poorer outcome (P = .02). The mutation was not identified in patients who had acute lymphoblastic leukemia (ALL) (n = 187), recurrent ALL (n = 49), acute myeloid leukemia (n = 44), lymphoma (n = 30), non-CPC central nervous system tumors (n = 26), Ewing sarcoma (n = 25), or rhabdomyosarcoma (n = 8). Among the tumors that were available for analysis, LOH with retention of the mutant allele was confirmed in 21 of 21 ACTs, in 2 of 2 CPCs, and in 2 of 3 osteosarcomas that were positive for R337H. CPCs and osteosarcomas that were positive for R337H had marked nuclear accumulation of p53.
  
  
  CONCLUSIONS
  The current findings demonstrated compellingly that the TP53 R337H mutation is associated not only with ACT but also with CPC and, to a lesser extent, with osteosarcoma, both of which are core-component tumors of the Li-Fraumeni syndrome.
authors.affiliation: Molecular Biology Laboratory, Boldrini Children's Center, Campinas, Sao Paulo, Brazil.
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Seidinger
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Mastellaro
authors.forename: Fernanda
authors.initials: F
authors.lastname: Paschoal Fortes
authors.forename: Juliana
authors.initials: J
authors.lastname: Godoy Assumpção
authors.forename: Izilda
authors.initials: I
authors.lastname: Aparecida Cardinalli
authors.forename: Mônica
authors.initials: M
authors.lastname: Aparecida Ganazza
authors.forename: Raul
authors.initials: R
authors.lastname: Correa Ribeiro
authors.forename: Silvia Regina
authors.initials: SR
authors.lastname: Brandalise
authors.forename: Simone
authors.initials: S
authors.lastname: Dos Santos Aguiar
authors.forename: José Andrés
authors.initials: JA
authors.lastname: Yunes
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics; D001938:Brazil; D016543:Central Nervous System Neoplasms / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D016545:Choroid Plexus Neoplasms / Q000235:genetics*; D005260:Female; D016158:Genes, p53; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics*; D015995:Prevalence