Concurrent sequence variation of TP53 and TP73 genes in anaplastic astrocytoma.
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.
Anselmo
N P
NP
Departamento de Genética, Laboratório de Oncogenética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Rey
J A
JA
Almeida
L O
LO
Custódio
A C
AC
Almeida
J R W
JR
Clara
C A
CA
Santos
M J
MJ
Casartelli
C
C
D000328:Adult; D001254:Astrocytoma / Q000235:genetics*; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins