MDM2 gene amplification in bone and soft-tissue tumors: association with tumor progression in differentiated adipose-tissue tumors.
We have studied 107 bone and soft-tissue sarcomas and 8 lipomas for amplification of the MDM2 gene. This gene was amplified in 3 out of 67 osteosarcomas, 3 out of 20 malignant fibrous histiocytomas, 4 out of 20 liposarcomas, and 4 out of 8 lipomas. The amplification was associated with overexpression of mRNA. In osteosarcomas, contrary to previous findings, all amplifications were observed in primary lesions. In liposarcomas, the amplification was seen exclusively in well-differentiated tumors with high frequency (4/5) but not in other subtypes (0/15). In addition, MDM2 amplification was also frequently found in deep-seated intra- or intermuscular lipomas (4/5). Hence, it is suggested that MDM2 amplification plays a significant role in the development of differentiated adipose-tissue tumors. Three well-differentiated liposarcomas with MDM2 amplification coexisted with high-grade dedifferentiated sarcomas, in which MDM2 amplification was also observed. Interestingly, in 2 of these cases, the grades of amplification correlated with the histological grades, indicating an important role of MDM2 overexpression in tumor progression.
Nakayama
T
T
Department of Orthopedic Surgery, Faculty of Medicine, Kyoto University, Japan.
Toguchida
J
J
Wadayama
B
B
Kanoe
H
H
Kotoura
Y
Y
Sasaki
M S
MS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D001859:Bone Neoplasms / Q000235:genetics*; D002454:Cell Differentiation / Q000502:physiology; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D016158:Genes, p53; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics; D006801:Humans; D008067:Lipoma / Q000235:genetics; D008080:Liposarcoma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins; D012516:Osteosarcoma / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000032:analysis; D012509:Sarcoma / Q000235:genetics; D012983:Soft Tissue Neoplasms / Q000235:genetics*
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2