Please use this identifier to cite or link to this item: http://dl.umsu.ac.ir/handle/10722/149792
Title: Telomere-mediated mitotic disturbances in immortalized ovarian epithelial cells reproduce chromosomal and breakpoints from ovarian carcinoma
Authors: Gisselsson, D;Lv, M;Tsao, SW;Man, C;Jin, C;Höglund, M;Yok, LK;Jin, Y
Year: 2005
Publisher: John Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/38250
United States
Description: Ovarian carcinomas (OCs) often exhibit highly complex cytogenetic changes. Abnormal chromosome segregation at mitosis is one potential mechanism for genomic rearrangements in tumors. In this study, OCs were demonstrated to have dysfunctional short telomeres, anaphase bridging, and multipolar mitoses with supernumerary centrosomes. When normal human ovarian surface epithelial (HOSE) cells were transfected with human papilloma virus 16 e6/e7 genes and subsequently driven into telomere crisis, the same set of mitotic disturbances occurred in a distinct sequence, initiated by telomere dysfunction, followed by anaphase bridging, and then supernumerary centrosomes and multipolar mitoses. The anaphase bridges resolved either by kinetochore-spindle detachment, corresponding to whole-chromosome losses in the HOSE karyotypes, or by extensive fragmentation of intercentromeric DNA sequences, corresponding to a high frequency of pericentromeric rearrangements. At later passages, the high degree of instability at telomere crisis was moderated by telomerase expression and centrosome coalescence, ultimately leading to a level of mitotic instability that was highly similar to that in OC cell lines and to complex karyotypes that were similar to those observed in high-grade OCs. This suggests that a significant proportion of the structural chromosome changes and genomic losses in OC are caused by a specific sequence of mitotic disturbances triggered by telomere crisis. That the model did not produce any of the whole-chromosome gains observed in OC indicates that these changes develop through a different mechanism. © 2004 Wiley-Liss, Inc.
URI: http://www.scopus.com/mlt/select.url?eid=2-s2.0-9644272618&selection=ref&src=s&origin=recordpage
http://hub.hku.hk/handle/10722/149792
Standard no: Genes Chromosomes And Cancer, 2005, v. 42 n. 1, p. 22-33
10.1002/gcc.20094
33
99340
WOS:000225367900003
1045-2257
1
15390185
eid_2-s2.0-9644272618
22
42
Appears in Collections:Department of Anatomy

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