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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Italiano A,Maire G,Sirvent N,Nuin PA,Keslair F,Foa C,Louis C,Aurias A,Pedeutour F

doi

10.1016/j.canlet.2008.08.025

subject

Has Abstract

pub_date

2009-01-18 00:00:00

pages

323-30

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(08)00655-1

journal_volume

273

pub_type

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