Characterization of centromere alterations in liposarcomas

Supernumerary ring and large marker chromosomes are a characteristic of aty pical lipomas and well-differentiated liposarcomas (ALP-WDLPS) and are comp osed of amplified 12q14-15 sequences in association with variable segments from other chromosomes. Although stably transmitted, these chromosomes cont ain centromeric alterations. showing no detectable alpha-satellite sequence s. We performed C-banding, fluorescence in situ hybridization, and immunost aining with anticentromere antibodies in 8 cases of liposarcomas with super numerary rings and large markers, including 5 ALP-WDLPS and 3 dedifferentia ted-LPS and high-grade LPS. Our results with alpha-satellite probes and ant i-CENPB antibodies confirm the lack of detectable alpha-satellite sequences in the five ALP-WDLPS supernumerary chromosomes, whereas centromeric activ ity was proved by the detection of kinetochores by using anti-CENPC antibod ies. In contrast, the high grade and dedifferentiated liposarcomas showed a different pattern. In 2 cases, amplified chromosome 12 sequences, includin g amplification of alpha-satellite 12 sequences in I case, were present on chromosomes with typical centromeres. In another case, the rings were simil ar to WDLPS-ALP rings, but a large marker contained a chromosome 5 centrome re and amplified alpha-satellite sequences from chromosome 8. ALP-WDLPS is the first example of a tumor class for which the presence of stable analpho id chromosomes is a constant and specific abnormality. Formation of newly d erived centromeres, so-called neocentromeres, could be an original and effe ctive way to maintain a selective advantage in neoplastic cells by conferri ng stability to the supernumerary chromosomes of ALP-WDLPS. The activation of normally non-centromeric sequences might be obtained by an epigenetic me chanism due to the peculiar chromatin conformation of these highly complex chromosomes. (C) 2000 Wiley-Liss, Inc.