Study on aneuploidy and p53 mutations in astrocytomas.
To determine whether a correlation exists between aneuploidy and p53 status in astrocytic tumors we analyzed 48 astrocytomas with different grades of malignancy for the presence of p53 mutations and aneuploidy of chromosomes 10 and 17 (Ch10, Ch17), known to be particularly involved with this type of tumor. We used polymerase chain reaction (PCR)-based denaturing gradient gel electrophoresis (DGGE) analysis on exons 5-8 of the p53 gene, and fluorescence in situ hybridization (FISH) analysis on interphase nuclei using chromosome specific pericentromeric probes, respectively. Our results showed that Ch10/Ch17 aneuploidy is a common early event in astrocytomas (90% of low grade tumors are aneuploid). p53 mutations and Ch17 aneuploidy are early events, but their incidence is not dependent on tumor grade. Loss of Ch10 is the only alteration that significantly correlates with tumor progression. No significant correlation between the presence of Ch10/Ch17 aneuploidy and p53 mutations was found. However, the coexistence of p53 mutations and aneuploidy, was observed in a subset of cases. The presence of p53 mutations appeared to be a significant predictor of a poor prognosis. In conclusion, genomic instability may or may not be associated with p53 mutations in astrocytomas, thus suggesting that other cellular determinants can also be responsible for the aneuploidy observed.
Campomenosi
P
P
CSTA-Mutagenesis Laboratory, National Institute for Cancer Research (IST) Genova, Italy.
Ottaggio
L
L
Moro
F
F
Urbini
S
S
Bogliolo
M
M
Zunino
A
A
Camoriano
A
A
Inga
A
A
Gentile
S L
SL
Pellegata
N S
NS
Bonassi
S
S
Bruzzone
E
E
Iannone
R
R
Pisani
R
R
Menichini
P
P
Ranzani
G N
GN
Bonatti
S
S
Abbondandolo
A
A
Fronza
G
G
D000328:Adult; D000368:Aged; D000782:Aneuploidy; D001254:Astrocytoma / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics*; D002872:Chromosome Deletion; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D012044:Regression Analysis