Characterization of centromere alterations in liposarcomas.
Supernumerary ring and large marker chromosomes are a characteristic of atypical lipomas and well-differentiated liposarcomas (ALP-WDLPS) and are composed of amplified 12q14-15 sequences in association with variable segments from other chromosomes. Although stably transmitted, these chromosomes contain centromeric alterations, showing no detectable alpha-satellite sequences. We performed C-banding, fluorescence in situ hybridization, and immunostaining with anti-centromere antibodies in 8 cases of liposarcomas with supernumerary rings and large markers, including 5 ALP-WDLPS and 3 dedifferentiated-LPS and high-grade LPS. Our results with alpha-satellite probes and anti-CENPB antibodies confirm the lack of detectable alpha-satellite sequences in the five ALP-WDLPS supernumerary chromosomes, whereas centromeric activity was proved by the detection of kinetochores by using anti-CENPC antibodies. In contrast, the high grade and dedifferentiated liposarcomas showed a different pattern. In 2 cases, amplified chromosome 12 sequences, including amplification of alpha-satellite 12 sequences in 1 case, were present on chromosomes with typical centromeres. In another case, the rings were similar to WDLPS-ALP rings, but a large marker contained a chromosome 5 centromere and amplified alpha-satellite sequences from chromosome 8. ALP-WDLPS is the first example of a tumor class for which the presence of stable analphoid chromosomes is a constant and specific abnormality. Formation of newly derived centromeres, so-called neocentromeres, could be an original and effective way to maintain a selective advantage in neoplastic cells by conferring stability to the supernumerary chromosomes of ALP-WDLPS. The activation of normally non-centromeric sequences might be obtained by an epigenetic mechanism due to the peculiar chromatin conformation of these highly complex chromosomes.
Sirvent
N
N
UF Recherche Clinique 0952, CHU de Nice, Université de Nice-Sophia Antipolis, France.
Forus
A
A
Lescaut
W
W
Burel
F
F
Benzaken
S
S
Chazal
M
M
Bourgeon
A
A
Vermeesch
J R
JR
Myklebost
O
O
Turc-Carel
C
C
Ayraud
N
N
Coindre
J M
JM
Pedeutour
F
F
D015139:Blotting, Southern; D002454:Cell Differentiation / Q000235:genetics; D002503:Centromere / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008080:Liposarcoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008297:Male; D014407:Tumor Cells, Cultured
D005819:Genetic Markers