title: Occurrence of Neuroblastoma among TP53 p.R337H Carriers.
abstract: The high incidence of adrenocortical tumors and choroid plexus carcinoma in children from South and Southeastern regions of Brazil is associated with the germline p.R337H mutation of TP53 gene. The concomitant occurrence of neuroblastoma and adrenocortical tumors in pediatric patients harboring the p.R337H mutation at our institution prompted us to investigate the putative association between p.R337H and pediatric neuroblastoma. Genomic DNA samples from 83 neuroblastoma patients referred to a single institution during the period of 2000-2014 were screened for the p.R337H mutation. Available samples from carriers were investigated for both nuclear p53 accumulation and loss of heterozigosity in tumor. Clinical data were obtained from medical records in order to assess the impact of 337H allele on manifestation of the disease. Seven out 83 neuroblastoma patients (8.4%) were carriers of the TP53 p.R337H mutation in our cohort. Immunohistochemical analysis of p.R337H-positive tumors revealed nuclear p53 accumulation. Loss of heterozigosity was not found among available samples. The presence of 337H allele was associated with increased proportion of stage I tumors. Our data indicate that in addition to adrenocortical tumors, choroid plexus carcinoma, breast cancer and osteosarcoma, genetic counseling and clinical surveillance should consider neuroblastoma as a potential neoplasia affecting p.R337H carriers.
authors.affiliation: Molecular Biology Laboratory, Boldrini Children's Center, Campinas, Sao Paulo, Brazil.
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Seidinger
authors.affiliation: Molecular Biology Laboratory, Boldrini Children's Center, Campinas, Sao Paulo, Brazil.
authors.forename: Fernanda Paschoal
authors.initials: FP
authors.lastname: Fortes
authors.affiliation: Pediatric Oncology Department, Boldrini Children's Center, Campinas, Sao Paulo, Brazil.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Mastellaro
authors.affiliation: Pathology Department, Boldrini Children's Center, Campinas, Sao Paulo, Brazil.
authors.forename: Izilda Aparecida
authors.initials: IA
authors.lastname: Cardinalli
authors.affiliation: Cytogenetics Laboratory, Boldrini Children's Center, Campinas, Sao Paulo, Brazil.
authors.forename: Lilian Girotto
authors.initials: LG
authors.lastname: Zambaldi
authors.affiliation: Pediatric Oncology Department, Boldrini Children's Center, Campinas, Sao Paulo, Brazil; Center for Research in Pediatrics, Faculty of Medical Sciences, State University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Simone Santos
authors.initials: SS
authors.lastname: Aguiar
authors.affiliation: Molecular Biology Laboratory, Boldrini Children's Center, Campinas, Sao Paulo, Brazil; Medical Genetics Department, Faculty of Medical Sciences, State University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: José Andrés
authors.initials: JA
authors.lastname: Yunes
mesh_terms: D000483:Alleles; D002675:Child, Preschool; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D009154:Mutation; D009447:Neuroblastoma / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis