Concurrent sequence variation of TP53 and TP73 genes in anaplastic astrocytoma
N P Anselmo1, J A Rey, L O Almeida
1Departamento de Genética, Laboratório de Oncogenética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Abstract:
Disruption or loss of tumor suppressor gene TP53 is implicated in the development or progression of almost all different types of human malignancies. Other members of the p53 family have been identified. One member, p73, not only shares a high degree of similarity with p53 in its primary sequence, but also has similar functions. Like p53, p73 can bind to DNA and activate transcription. Using PCR-SSCP and gene sequencing, we analyzed the TP53 and TP73 genes in a case of a grade III anaplastic astrocytoma that progressed to glioblastoma. We found a deletion of AAG at position 595-597 of TP53 (exon 6), resulting in the deletion of Glu 199 in the protein and a genomic polymorphism of TP73, identified as an A-to-G change, at position E8/+15 at intron 8 (IVS8-15A>G). The mutation found at exon 6 of the gene TP53 could be associated with the rapid tumoral progression found in this case, since the mutated p53 may inactivate the wild-type p53 and the p73alpha protein, which was conserved here, leading to an increase in cellular instability.
Insights
Tumor suppressor gene TP53 mutations, like the exon 6 deletion found in this anaplastic astrocytoma, can drive rapid glioblastoma progression. This TP53 alteration may also inactivate protective p53 and p73alpha proteins.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The tumor suppressor gene TP53 is crucial in preventing human malignancies.
- The p53 family includes p73, which shares sequence similarity and functional roles with p53.
- p53 and p73 can bind DNA and activate transcription, suggesting roles in tumor suppression.
Observation:
- TP53 and TP73 genes were analyzed in a grade III anaplastic astrocytoma that progressed to glioblastoma.
- A deletion of AAG at positions 595-597 in TP53 (exon 6) was identified, leading to the loss of Glu 199.
- A genomic polymorphism (A-to-G change) was found in TP73 at intron 8 (IVS8-15A>G).
Findings:
- The TP53 exon 6 mutation (deletion of Glu 199) was observed in the anaplastic astrocytoma progressing to glioblastoma.
- This TP53 mutation may lead to the inactivation of wild-type p53 and p73alpha.
- The TP73 gene exhibited a common genomic polymorphism.
Implications:
- The identified TP53 mutation could be linked to the rapid tumor progression observed in this case.
- Inactivation of p53 and p73alpha by the mutated p53 may increase cellular instability.
- Understanding these genetic alterations is vital for comprehending glioblastoma development and progression.
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