Gains and complex rearrangements of the 12q13-15 chromosomal region in ordinary lipomas: the "missing link" between lipomas and liposarcomas?
Well-differentiated liposarcomas (WDLPS) classically contain high-level amplification of 12q14-15 sequences, including the MDM2 and CDK4 genes, while lipomas are characterized by simple structural chromosome aberrations often involving HMGA2 at 12q15. Previous studies have shown that low-level gain of the 12q14-15 region, such as trisomy 12 and 12q15-24 duplication, might be sufficient for the development of minimal atypia and formation of WDLPS. Moreover, because some features, such as overexpression of HMGA2, are shared by both lipomas and WDLPS, it has been hypothesized that lipomas and WDLPS may form a genetic and morphological continuum. We report here the results of molecular cytogenetic analysis of 8 lipomas that had unusual chromosomal features resulting in gains of 12q14-15. While 3 cases had simple numerical rearrangements (trisomy 12) or structural rearrangements (unbalanced translocations with 12q gains), 5 cases were particularly intriguing because of peculiar features such as giant chromosomes, supernumerary chromosomes or neocentromeres that usually are the hallmark of WDLPS. Gain of 12q14-15 sequences including extra copies of MDM2 and CDK4 were detected by fluorescence in situ hybridization analysis in all analyzed cases but no expression of MDM2 and CDK4 was observed suggesting that these genomic imbalances had no functional consequence. We observed rearrangements of HMGA2 in 5 out 8 cases. Altogether, our results indicate that moderate gains of 12q are not always associated with a malignant phenotype, and that some intermediary forms exist between classical lipomas and classical WDLPS. Some of these intermediary forms may correspond to a genomic premalignant condition while some may have no malignant potential.
Italiano
Antoine
A
Faculty of Medicine, Laboratory of Solid Tumors Genetics, Nice University Hospital and CNRS UMR 6543, Nice, France.
Cardot
Nathalie
N
Dupré
Florence
F
Monticelli
Isabelle
I
Keslair
Frédérique
F
Piche
Marjorie
M
Mainguené
Claire
C
Coindre
Jean-Michel
JM
Pedeutour
Florence
F
D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics; D005260:Female; D025743:HMGA2 Protein / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008067:Lipoma / Q000235:genetics* / Q000473:pathology*; D008080:Liposarcoma / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D014178:Translocation, Genetic; D014314:Trisomy
D025743:HMGA2 Protein; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4