Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors.
Supernumerary ring or giant rod marker chromosomes are a characteristic of well-differentiated liposarcomas (WDLPS) and atypical lipomas (ALP) and are often observed as the sole cytogenetic abnormality, but are rare in lipomas. Using a combination of different methods, we extensively investigated the structure and composition of rings and giant rods in a series of 17 WDLPS-ALP samples and three intra- or intermuscular lipomas (IMLP), revealing a unique combination of particular features strikingly related to these tumors. Although the rings and rods displayed in vitro and in vivo stability, the presence of alpha-satellites could not be detected on these supernumerary structures. Comparative genomic hybridization analysis, in combination with fluorescence in situ hybridization, identified the chromosomal regions contributing to the formation of these chromosomes: in WDLPS-ALP, all carried amplifications of 12q 14-15 and the MDM2 gene, with variable other noncontiguous regions. In the three IMLP, the rings consistently carried amplifications of 12q15-21 and 1q21, but increased copies of MDM2 were found in only one case. Other genes located more proximal in 12q14-15 were amplified in several WDLPS-ALP, but showed a normal copy number in IMLP. Furthermore, the immunohistochemical expression of the MDM2 protein was detected in most (12/14) WDLPS-ALP, in 1-30% of the cells, but never in IMLP. These supernumerary chromosomes represent a peculiar kind of amplification structure, midway between double minute chromosomes and homogeneously staining regions, but the mechanisms underlying the formation of these structures remain obscure.
Pedeutour
F
F
UMR 6549, CNRS UNSA, Université de Nice-Sophia Antipolis, France.
Forus
A
A
Coindre
J M
JM
Berner
J M
JM
Nicolo
G
G
Michiels
J F
JF
Terrier
P
P
Ranchere-Vince
D
D
Collin
F
F
Myklebost
O
O
Turc-Carel
C
C
D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D002503:Centromere / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D002869:Chromosome Aberrations / Q000235:genetics / Q000473:pathology*; D025063:Chromosome Disorders; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D015342:DNA Probes; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008080:Liposarcoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018205:Neoplasms, Adipose Tissue / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D012303:Ring Chromosomes
D015342:DNA Probes; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases