Molecular analysis for p53 and mdm2 in intracranial germ cell tumors.
Intracranial germ cell tumors (ICGTs) are uncommon neoplasms. The histological appearance of ICGTs is indistinguishable from that of the usual testicular germ cell tumors (TGTs). Recently, several reports have associated molecular abnormalities of p53 and mdm2 in TGTs with their malignancies. However, whether ICGTs are associated with molecular abnormalities is still unknown. We analyzed a series of 16 ICGTs for mutations in the TP53 gene by single-strand conformation polymorphisms, and for amplification of the MDM2 gene using differential PCR. In addition, the same 16 tumors were examined for p53 and mdm2 protein overexpression using antibodies directed against p53 [monoclonal antibodies (mAb) 1801 and DO7] and mdm2 (IF2), respectively. Twelve (75%) and 2 (13%) of the 16 ICGTs reacted with DO7 and PAb1801, respectively, and 1 (6%) carried a TP53 gene mutation. Thirteen (81%) of the 16 ICGTs reacted with IF2, and 3 (19%) carried MDM2 gene amplification. The less frequent TP53 gene mutation compared with MDM2 gene amplification, and the frequently expressed p53 and mdm2 protein, are similar to the case for TGTs. It is tempting to speculate that ICGTs might have the same cellular origins as TGTs with abnormalities in p53 and mdm2, which could play an important role of tumorigenesis.
Iwato
M
M
Department of Neurosurgery, Kanazawa University School of Medicine, Japan.
Tachibana
O
O
Tohma
Y
Y
Nitta
H
H
Hayashi
Y
Y
Yamashita
J
J
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005784:Gene Amplification; D018237:Germinoma / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2