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Horm Metab Res 2005; 37(4): 231-235
DOI: 10.1055/s-2005-861373
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Inheritance of R337H p53 Gene Mutation in Children with Sporadic Adrenocortical Tumor

F.  Sandrini1 , D.  P.  Villani3 , S.  Tucci2 , A.  C.  Moreira1 , M.  de Castro1 , L.  L.  K.  Elias3
  • 1 Department of Internal Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, SP, Brazil
  • 2 Department of Surgery and Anatomy, School of Medicine of Ribeirao Preto, University of Sao Paulo, SP, Brazil
  • 3 Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, SP, Brazil
Further Information

Publication History

Received 23 July 2004

Accepted after revision 21 October 2004

Publication Date:
13 June 2005 (online)

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Abstract

Adrenocortical tumors (ACTs) are frequent in Brazil. The mechanisms of adrenal tumorigenesis remain poorly established; the R337H germline mutation in the p53 gene has previously been associated with ACTs in Brazilian children. We investigated the frequency and inheritance of R337H p53 mutation as well as genotype and phenotype correlation in 21 children and 5 adult patients with ACTs. DNA was extracted from peripheral blood cells and/or tumor tissue for sequencing exon 10 of the p53 gene. Nine sets of parents of patients with p53 mutation were also submitted to mutational analysis. Virilization was the most common clinical sign in children with or without Cushing’s syndrome. Two members of the adult group showed asymptomatic adrenal incidentalomas, two showed virilization, and one presented with Cushing’s syndrome. Sixteen children with ACTs had peripheral blood available, and twelve of them (75 %) showed the heterozygous R337H p53 gene mutation. The R337H mutation was found in fifteen samples of the nineteen tumor specimens available (78.9 %). Among the nine sets of parents of the patients with R337H mutation, eight showed the same mutation with heterozygosity in one of the parents. None of the parents showed ACTs or any other neoplasia at the time of the study. Only one adult patient with an ACT revealed the same R337H p53 germline mutation. There was no association between the presence of germline or tissue R337H p53 mutation and malignancy at diagnosis. We confirmed the high frequency of R337H p53 mutation in Brazilian children with sporadic ACTs. The R337H p53 mutation was inherited from one of the parents of the patients, and there was no association between the presence of this mutation and tumor malignancy in children. The founder effect of R337H p53 mutation and the role of environmental mutagens contributing to the geographical clustering and high prevalence of ACTs in Brazilian children remain to be established.

Key words

p53 mutation - DNA sequencing - Adrenocortical tumor - Inheritance

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Lucila Leico Kagohara Elias

Department of Physiology · School of Medicine of Ribeirao Preto · University of Sao Paulo

Avenida dos Bandeirantes, 3900 - Monte Alegre · CEP: 14049-900 Ribeirao Preto - SP · Brazil ·

Phone: + 55 16 602 3057

Fax: + 55 16 633 0017

Email: llelias@fmrp.usp.br

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