[Comparative genomic hybridization (CGH) for detecting a heretofore undescribed amplified chromosomal segment in high-grade medullary osteosarcoma].
Osteosarcoma is one of the most commonly biopsied primary tumor of bone. High-grade osteosarcomas in particular exhibit a wide spectrum of cytogenetic changes. Molecular cytogenetic studies on osteosarcomas have shown that genomic amplification, especially of both the TP53-binding MDM2 gene and the flanking SAS gene, plays an important role in the biology of these tumors. We applied CGH in order to obtain a global view of DNA-sequence losses and gains in osteosarcoma. CGH was performed on 20 high-grade medullary osteosarcomas (13 primary tumors prior to chemotherapy, 5 tumors after chemotherapy, 2 established cell lines [MB63, HOS58]) using genomic DNA of snap-frozen tumor specimens. CGH revealed DNA copy number aberrations, mostly gains, in all the tumors studied with an average of 18.5 aberrations/tumor (range 8-32). High-level amplifications were observed in all cases (average 4.1 amplifications/tumor [range 1-10]). Amplicons affecting at least five tumors were mapped to 1p21-31 (9/20 cases), 3q25-qter (6/20), 6p12-21 (6/20), 8q12-qter (10/20), 12p11-12 (9/20), 12q12-15 (enclosing MDM2 and SAS loci, 7/20). Losses were most frequently seen at 3p, 10q, 11p and 13 (all 10/20). In conclusion, our CGH data indicated that genomic amplification plays an important role in the biology of osteosarcoma. CGH demonstrated the complexity of genetic aberrations in osteosarcomas. The detection of novel non-random DNA amplifications in our study has defined regions for further targeted molecular genetic research aimed at identifying those oncogenes that are characteristic of osteosarcoma development.
Brinkschmidt
C
C
Institut für Pathologie, Westfälischen Wilhelms-Universität Münster.
Blasius
S
S
Bürger
H
H
Simon
R
R
Diallo
R
R
Battmann
A
A
Winkelmann
W
W
Böcker
W
W
Dockhorn-Dworniczak
B
B
D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D006801:Humans; D019656:Loss of Heterozygosity; D009687:Nuclear Proteins; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D011519:Proto-Oncogenes; D014407:Tumor Cells, Cultured
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2