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An Inherited Mutation Outside the Highly Conserved DNA-Binding Domain of the p53 Tumor Suppressor Protein in Children and Adults with Sporadic Adrenocortical Tumors
Mutations of the p53 tumor suppressor gene are the single most common genetic alterations in human cancers. Recently, a distinct nucleotide substitution was identified in exon 10 of the p53 gene, leading to an Arg337His mutation in 97% of children with adrenocortical tumors from Southern Brazil. In...
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Published in: | The journal of clinical endocrinology and metabolism 2001-10, Vol.86 (10), p.4970-4973 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that cite this one |
Online Access: | Get full text |
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Summary: | Mutations of the p53 tumor suppressor gene are the single
most common genetic alterations in human cancers. Recently, a distinct
nucleotide substitution was identified in exon 10 of the p53 gene,
leading to an Arg337His mutation in 97% of children with
adrenocortical tumors from Southern Brazil. In the present study, we
investigated the presence of this mutation in a larger series of 55
patients (37 adults and 18 children) with benign and malignant sporadic
adrenocortical tumors. None of the patients had family cancer histories
that conformed to the criteria for Li-Fraumeni syndrome. Twenty-one
asymptomatic close relatives of patients with p53 mutations and 60
normal unrelated individuals were also studied. The missense Arg337His
mutation was identified in 19 patients (14 children and 5 adults), and
8 of 11 cases studied had LOH. Among the 19 patients with the Arg337His
mutation, only one boy and three adults showed fatal evolution or
recurrent metastases. This mutation was also identified in heterozygous
state in asymptomatic first-degree relatives of the patients,
indicating that Arg337His mutation was inherited in most cases. In
contrast, this mutation was not found in 120 alleles of normal
unrelated controls. In conclusion, the germ line Arg337His mutation of
p53 protein is present at a high frequency (77.7%) in children with
benign or malignant sporadic adrenocortical tumors, but it is not
restricted to the pediatric group, since 13.5% of adults with
adrenocortical tumors also had this mutation. The presence of this
mutation was related to unfavorable prognosis in most of the adults,
but not in the children with adrenocortical tumors. |
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ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jcem.86.10.7957 |