Detection of Novel Germ-line p53 Mutations in Diverse-Cancer-Prone Families Identifiled by Selecting Patients With Childhood Adrencortical Carcinoma
| Autor: | Yukiko Tsunematsu, Hideaki Mizoguchi, Yoshiaki Hirata, Jun Yokota, Yuichi Sameshima, Masaaki Terada, Keisei Kawa-Ha, Taiji Tsukamoto, Takashi Sugimura, Shaw Watanabe |
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| Rok vydání: | 1992 |
| Předmět: |
Proband
Cancer Research DNA Mutational Analysis Molecular Sequence Data Gene mutation Biology medicine.disease_cause Polymerase Chain Reaction Genetic analysis Li-Fraumeni Syndrome Exon medicine Humans Amino Acid Sequence Transversion Gene Genes Dominant Genetics Mutation Base Sequence Carcinoma Genes p53 Adrenal Cortex Neoplasms Pedigree genomic DNA Oligodeoxyribonucleotides Oncology Immunology Tumor Suppressor Protein p53 |
| Zdroj: | JNCI Journal of the National Cancer Institute. 84:703-707 |
| ISSN: | 1460-2105 0027-8874 |
| DOI: | 10.1093/jnci/84.9.703 |
| Popis: | BACKGROUND Germ-line p53 mutations appear to be inherited among the members of families diagnosed with Li-Fraumeni syndrome (LFS). The mutations detected in those families to date have been clustered in exon 7 of the p53 gene and, typically, have been single-base substitutions resulting in amino acid changes. PURPOSE Our aim was to define the spectrum of p53 mutations associated with LFS. METHODS From seven cancer-prone families identified by selecting members with childhood adrenocortical carcinoma as probands, we chose two families, each of which had two members from whom specimens could be obtained for genetic analysis. To detect germ-line p53 gene mutations in these individuals, we performed polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis with Taq polymerase and oligonucleotide primers specific for p53 gene sequences. Genomic DNA extracted from fresh tissue samples and paraffin-embedded tumor samples was amplified, denatured, and electrophoresed on neutral polyacrylamide gels. PCR amplification was also carried out using total RNA from adrenocortical carcinoma samples of the proband in family 1. PCR products were purified, subcloned, and sequenced. RESULTS We detected novel germ-line p53 mutations in affected members of both cancer-prone families. In the proband of family 1, a single-base deletion was detected at the first nucleotide of codon 307 in exon 8 of the p53 gene, resulting in a premature stop codon in exon 10. In family 2, we detected an A to C transversion at the second nucleotide of codon 286 in exon 8, both in DNA isolated from the adrenocortical tumor of the proband and in DNA isolated from the astrocytoma of the proband's father. This single-base substitution resulted in an amino acid substitution of alanine for glutamic acid. Both of these mutations are located outside the highly conserved region of the p53 gene where mutations in patients with LFS have been reported previously. CONCLUSION Our results indicate that a wide range of germ-line p53 mutations is inherited in members of diverse-cancer-prone families. |
| Databáze: | OpenAIRE |
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