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Low frequency of the p53 gene mutations in neuroblastoma
Background:
The p53 gene frequently is affected by point mutations, rearrangements, or deletions that contribute to the genesis or progression of a wide variety of human adult solid tumors; however, to the authors' knowledge, this gene alteration has not been analyzed in neuroblastoma.
Methods:
Genomic DNA samples from 20 children with neuroblastoma, including 16 patients with advanced disease, were screened for the presence of mutations in exons 5-9 of the p53 gene, where over 90% of mutations have been reported to be located in human cancer. The screening technique employed polymerase chain reaction/single-strand conformation polymorphism analysis followed by direct DNA sequencing.
Results:
Heterozygous mutations were detected in 2 of the 20 cases. A silent mutation (T to G transversion) at codon 172 and a missense mutation (G to T transversion) at codon 259 were found in patients with Stage II and Stage IV disease, respectively. Thus, p53 mutations were found to occur in neuroblastoma, but at a low frequency (2 of 20).
Conclusions:
Our data suggest that in a minority of neuroblastomas, p53 gene mutations may play a contributing role in tumorigenesis, but other genes presumably play a major role in this tumor.
Insights
p53 gene mutations are rare in neuroblastoma, found in only 2 of 20 pediatric cases. These alterations may contribute to tumor development in a small subset of patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The p53 gene is frequently altered in adult solid tumors.
- p53 gene alterations have not been previously analyzed in neuroblastoma.
Purpose of the Study:
- To investigate the presence and frequency of p53 gene mutations in neuroblastoma.
- To determine if p53 gene alterations play a role in neuroblastoma development.
Main Methods:
- Screening of genomic DNA from 20 neuroblastoma patients for p53 mutations (exons 5-9).
- Utilized polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) and direct DNA sequencing.
Main Results:
- Heterozygous p53 mutations were detected in 2 out of 20 neuroblastoma cases.
- A silent mutation at codon 172 (Stage II) and a missense mutation at codon 259 (Stage IV) were identified.
- p53 mutations occur at a low frequency (10%) in this neuroblastoma cohort.
Conclusions:
- p53 gene mutations may contribute to tumorigenesis in a minority of neuroblastomas.
- Other genes are likely to play a more significant role in the majority of neuroblastoma cases.