title: Variability of origin for the neocentromeric sequences in analphoid supernumerary marker chromosomes of well-differentiated liposarcomas.
abstract: Well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas are cytogenetically characterized by the presence of supernumerary ring or giant chromosomes containing amplified material from the 12q14-15 region. These chromosomes contain neocentromeres, which are able to bind the kinetochore proteins and to ensure a stable mitotic transmission although they do not show detectable alpha-satellite sequences. WDLPS is the sole solid tumor for which the presence of a neocentromere is a consistent and specific feature. By immunostaining with anti-centromere antibodies in combination with FISH analysis (immunoFISH) in four cases of WDLPS, we have shown that sequences from the region 12q14-21 region were not located at the neocentromere site. In addition, we have microdissected the neocentromeric region from a giant supernumerary chromosome in the 94T778 WDLPS cell line. By using immunoFISH and positional cloning we have shown that the neocentromere of this cell line originated from a region at 4p16.1, rich in AT sequences and in long interspersed nucleotide element (LINE)1, that was co-amplified with 12q14-15. We have observed that this 4p sequence was not involved in the neocentromere of the supernumerary giant chromosome present in the 93T449 WDLPS cell line derived from a metachronous recurrence of the same primary WDLPS than 94T778. Altogether, these results indicate that the neocentromeres in WDLPS originate from amplified chromosomal regions other than 12q14-15 and do not involve a specific and recurrent DNA sequence. These sequences might be activated for centromeric function by epigenetic mechanisms.
authors.affiliation: Laboratory of Solid Tumors Genetics, Nice University Hospital and CNRS UMR 6543, Faculty of Medicine, 28 avenue de Valombrose, 06107 Nice, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Italiano
authors.forename: Georges
authors.initials: G
authors.lastname: Maire
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sirvent
authors.forename: Paulo A S
authors.initials: PA
authors.lastname: Nuin
authors.forename: Frédérique
authors.initials: F
authors.lastname: Keslair
authors.forename: Cyril
authors.initials: C
authors.lastname: Foa
authors.forename: Caroline
authors.initials: C
authors.lastname: Louis
authors.forename: Alain
authors.initials: A
authors.lastname: Aurias
authors.forename: Florence
authors.initials: F
authors.lastname: Pedeutour
mesh_terms: D002460:Cell Line; D002503:Centromere / Q000648:ultrastructure*; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000648:ultrastructure*; D003001:Cloning, Molecular; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008080:Liposarcoma / Q000235:genetics* / Q000473:pathology; D020084:Long Interspersed Nucleotide Elements; D008677:Metaphase; D042282:Microdissection; D008938:Mitosis