{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T21:46:40Z","timestamp":1757540800055,"version":"3.37.3"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,9,23]],"date-time":"2004-09-23T00:00:00Z","timestamp":1095897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007687","name":"Swedish Medical Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007687","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003173","name":"Crafoord Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003173","id-type":"DOI","asserted-by":"crossref"}]},{"name":"John and Augusta Persson Foundation"},{"name":"Kadoorie Charitable Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 <jats:italic>e6\/e7<\/jats:italic> 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\u2010spindle detachment, corresponding to whole\u2010chromosome 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\u2010grade 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\u2010chromosome gains observed in OC indicates that these changes develop through a different mechanism. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20094","type":"journal-article","created":{"date-parts":[[2004,9,23]],"date-time":"2004-09-23T16:04:02Z","timestamp":1095955442000},"page":"22-33","source":"Crossref","is-referenced-by-count":30,"title":["Telomere\u2010mediated mitotic disturbances in immortalized ovarian epithelial cells reproduce chromosomal losses and breakpoints from ovarian carcinoma"],"prefix":"10.1002","volume":"42","author":[{"given":"David","family":"Gisselsson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai\u2010Wha","family":"Tsao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia","family":"Man","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mattias","family":"H\u00f6glund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yok Lam","family":"Kwong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuesheng","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,9,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/35020592"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1067\/S0002-9378(03)00579-9"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110380"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.170093297"},{"key":"e_1_2_6_6_1","first-page":"7075","article-title":"The human papillomavirus type 16 E6 and E7 oncoproteins independently induce numerical and structural chromosome instability","volume":"62","author":"Duensing S","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/58.2.209"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(200002)27:2<183::AID-GCC10>3.0.CO;2-P"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.211357798"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600438"},{"key":"e_1_2_6_11_1","first-page":"5379","article-title":"Characterization of a human ovarian carcinoma cell line (NIH:OVCAR\u20103) with androgen and estrogen receptors","volume":"43","author":"Hamilton TC","year":"1983","journal-title":"Cancer Res"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/346866a0"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.11.052"},{"key":"e_1_2_6_14_1","first-page":"3378","article-title":"Ovarian carcinoma develops through multiple modes of chromosomal evolution","volume":"63","author":"H\u00f6glund M","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2003.09.007"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5406.1321"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069523"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.5.685"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/25292"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.032479999"},{"key":"e_1_2_6_21_1","first-page":"951","article-title":"Expression profile of senescence\u2010associated beta\u2010galactosidase and activation of telomerase in human ovarian surface epithelial cells undergoing immortalization","volume":"13","author":"Litaker JR","year":"1998","journal-title":"Int J Oncol"},{"key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/genetics\/23.4.315","article-title":"The production of homozygous deficient tissues with mutant characteristics by means of the aberrant behavior of ring\u2010shaped chromosomes","volume":"23","author":"McClintock B","year":"1938","journal-title":"Genetics"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.4.483"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.2870100402"},{"key":"e_1_2_6_25_1","unstructured":"MitelmanF JohanssonB MertensF.2004. 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