Genomic instability and p53 alterations in patients with malignant glioma.
The purpose of this study was to detect the level of genomic instability and p53 alterations in anaplastic astrocytoma and primary glioblastoma patients, and to evaluate their impact on glioma pathogenesis and patients outcome. AP-PCR DNA profiling revealed two types of genetic differences between tumor and normal tissue: qualitative changes which represent accumulation of changes in DNA sequence and are the manifestation of microsatellite and point mutation instability (MIN-PIN) and quantitative changes which represent amplifications or deletions of existing chromosomal material and are the manifestation of chromosomal instability (CIN). Both types of alterations were present in all analyzed samples contributing almost equally to the total level of genomic instability, and showing no differences between histological subtypes. p53 alterations were detected in 40% of samples, predominantly in anaplastic astrocytoma. The higher level of genomic instability was observed in elderly patients (>50 years) and patents with primary glioblastoma. Level of genomic instability had no impact on patients' survival, while presence of p53 alterations seemed to be a favorable prognostic factor in this case. Our results indicate that extensive genomic instability is one of the main features of malignant gliomas.
Institute for Biological Research, Sinisa Stankovic, Department of Neurobiology, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
Vedrana
V
Milinkovic
Jasna
J
Bankovic
Miodrag
M
Rakic
Nebojsa
N
Milosevic
Tijana
T
Stankovic
Milos
M
Jokovic
Zorica
Z
Milosevic
Milica
M
Skender-Gazibara
Ana
A
Podolski-Renic
Milica
M
Pesic
Sabera
S
Ruzdijic
Nikola
N
Tanic
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D042822:Genomic Instability; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D005910:Glioma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D017354:Point Mutation; D055771:Serbia / Q000453:epidemiology; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53