Molecular genetic analysis of non-astrocytic gliomas.
OBJECTIVE
Oligodendroglial tumours follow genetic pathways different from but overlapping with those of astrocytic tumours. The aim of this study was to examine whether major genetic events such as loss of chromosome 10 and p53 mutation found in astrocytic gliomas are also involved in the development and anaplastic transformation of non-astrocytic gliomas and to correlate the findings with histopathological subtypes of these tumours.


RESULTS
Sixty-one formalin-fixed, paraffin-embedded oligodendroglial and ependymal tumours (16 oligodendrogliomas, 12 anaplastic oligodendrogliomas, seven oligoastrocytomas, 24 ependymomas and two anaplastic ependymomas) were examined for allelic deletions on chromosome 10q23 and 10q25-26 regions, mutations of PTEN/MMAC1 and p53, MDM2 gene amplification and apoptosis. The frequencies of allelic deletions at marker D10S2491 (which mapped within PTEN/MMAC1) and between markers D10S209 and D10S587 (where DMBT1 was located) were found to be < 30% in both types of non-astrocytic gliomas. High frequency of allelic deletions was detected at marker D10S215 (80%) at the proximal 10q23 region in both oligodendroglial and ependymal tumours and between markers D10S216 (42%) and D10S169 (67%) at distal 10q25-26 region in oligodendroglial tumours. No mutations of PTEN/MMAC1 were found. p53 mutations were detected in three oligoastrocytomas and one ependymoma; three out of five mutations were found in exon 4. MDM2 gene amplification was found in one ependymoma harbouring wild-type p53. The apoptotic index was lower in p53-mutated tumours than in tumours with wild-type p53.


CONCLUSIONS
The telomeric end of chromosome 10q could be involved in the development and anaplastic transformation of oligodendroglial tumours. Mutations of PTEN/MMAC1 and p53, amplification of the MDM2 gene and allelic loss on chromosome 10q do not play a major part in the pathogenesis or anaplastic transformation of oligodendrogliomas and ependymal tumours.
Tong
C Y
CY
Department of Anatomical & Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
Ng
H K
HK
Pang
J C
JC
Hui
A B
AB
Ko
H C
HC
Lee
J C
JC
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002879:Chromosomes, Human, Pair 10; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D025521:Tumor Suppressor Proteins
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human