title: Impact of neonatal screening and surveillance for the TP53 R337H mutation on early detection of childhood adrenocortical tumors.
abstract: OBJECTIVE
  The incidence of pediatric adrenocortical tumors (ACTs) is remarkably high in southern Brazil, where more than 90% of patients carry the germline TP53 mutation R337H. We assessed the impact of early detection of this mutation and of surveillance of carriers.
  
  
  METHODS
  Free newborn screening was offered at all hospitals in the state of Paraná. Parents of positive newborns were tested, and relatives in the carrier line were offered screening. Positive newborns and their relatives age < 15 years were offered surveillance (periodic clinical, laboratory, and ultrasound evaluations). ACTs detected by imaging were surgically resected.
  
  
  RESULTS
  Of 180,000 newborns offered screening, 171,649 were screened, and 461 (0.27%) were carriers. As of April 2012, ACTs had been diagnosed in 11 of these carriers but in only two neonatally screened noncarriers (P < .001); six patient cases were identified among 228 carrier relatives age < 15 years (total, 19 ACTs). Surveillance participants included 347 (49.6%) of 699 carriers. Tumors were smaller in surveillance participants (P < .001) and more advanced in nonparticipants (four with stage III disease; two deaths). Neonatally screened carriers also had neuroblastoma (n = 1), glioblastoma multiforme (n = 1), choroid plexus carcinoma (n = 2), and Burkitt lymphoma (n = 1). Cancer histories and pedigrees were obtained for 353 families that included 1,704 identified carriers. ACTs were the most frequent cancer among carrier children (n = 48).
  
  
  CONCLUSIONS
  These findings establish the prevalence of the TP53 R337H mutation in Paraná state and the penetrance of ACTs among carriers. Importantly, screening and surveillance of heterozygous carriers are effective in detecting ACTs when readily curable.
authors.affiliation: Pelé Pequeno Príncipe Research Institute, Avenida Silva Jardim, 1632, Água Verde, Curitiba, PR 80.250-200, Brazil.
authors.forename: Gislaine
authors.initials: G
authors.lastname: Custódio
authors.forename: Guilherme A
authors.initials: GA
authors.lastname: Parise
authors.forename: Nilton
authors.initials: N
authors.lastname: Kiesel Filho
authors.forename: Heloisa
authors.initials: H
authors.lastname: Komechen
authors.forename: Cesar C
authors.initials: CC
authors.lastname: Sabbaga
authors.forename: Roberto
authors.initials: R
authors.lastname: Rosati
authors.forename: Leila
authors.initials: L
authors.lastname: Grisa
authors.forename: Ivy Z S
authors.initials: IZ
authors.lastname: Parise
authors.forename: Mara A D
authors.initials: MA
authors.lastname: Pianovski
authors.forename: Carmem M C M
authors.initials: CM
authors.lastname: Fiori
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Ledesma
authors.forename: José Renato S
authors.initials: JR
authors.lastname: Barbosa
authors.forename: Francisco R O
authors.initials: FR
authors.lastname: Figueiredo
authors.forename: Elis R
authors.initials: ER
authors.lastname: Sade
authors.forename: Humberto
authors.initials: H
authors.lastname: Ibañez
authors.forename: Sohaila B I
authors.initials: SB
authors.lastname: Arram
authors.forename: Sérvio T
authors.initials: ST
authors.lastname: Stinghen
authors.forename: Luciano R
authors.initials: LR
authors.lastname: Mengarelli
authors.forename: Mirna M O
authors.initials: MM
authors.lastname: Figueiredo
authors.forename: Danilo C
authors.initials: DC
authors.lastname: Carvalho
authors.forename: Sylvio G A
authors.initials: SG
authors.lastname: Avilla
authors.forename: Thiago D
authors.initials: TD
authors.lastname: Woiski
authors.forename: Lisiane C
authors.initials: LC
authors.lastname: Poncio
authors.forename: Geneci F R
authors.initials: GF
authors.lastname: Lima
authors.forename: Roberto
authors.initials: R
authors.lastname: Pontarolo
authors.forename: Enzo
authors.initials: E
authors.lastname: Lalli
authors.forename: Yinmei
authors.initials: Y
authors.lastname: Zhou
authors.forename: Gerard P
authors.initials: GP
authors.lastname: Zambetti
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
authors.forename: Bonald C
authors.initials: BC
authors.lastname: Figueiredo
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D001938:Brazil / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing / Q000379:methods*; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods; D010375:Pedigree; D018570:Risk Assessment; D017678:Sex Distribution; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53