{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:56:20Z","timestamp":1787014580726,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,7,5]],"date-time":"2007-07-05T00:00:00Z","timestamp":1183593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:p>\n                    Glioblastoma multiforme (GBM) and other high\u2010grade brain tumours are typically characterized by complex chromosome abnormalities and extensive intratumour cytogenetic heterogeneity. The mechanisms behind this diversity have been little explored. In this study, we analysed the pattern of chromosome segregation at mitosis in 20 brain tumours. We found an abnormal segregation of chromatids at mitosis through anaphase bridging (10\u201325% of anaphase cells) in all 10 GBMs. Anaphase bridging was also found in two medulloblastomas (7\u201315%), one anaplastic astrocytoma (17%) and one oligodendroglioma (6%). These tumours showed a relatively high degree of cytogenetic complexity and heterogeneity. In contrast, cell division abnormalities were not found in low\u2010grade brain tumours with less complex karyotypes, including two pilocytic astrocytomas and two ependymomas. Further analysis of two GBMs by fluorescence\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization with telomeric repeat probes revealed excessive shortening of TTAGGG repeats, indicating dysfunctional protection of chromosome ends. In xenografts established from these GBMs, there was a gradual reduction in cytogenetic heterogeneity through successive passages as the proportion of abnormally short telomeres was reduced and the frequency of anaphase bridges decreased from &gt;25% to 0. However, bridging could be reintroduced in late\u2010passage xenograft cells by pharmacological induction of telomere shortening, using a small\u2010molecule telomerase inhibitor. Telomere\u2010dependent abnormal segregation of chromosomes at mitosis is thus a common phenomenon in high\u2010grade brain tumours and may be one important factor behind cytogenetic intratumour diversity in GBM.\n                  <\/jats:p>","DOI":"10.1111\/j.1365-2990.2007.00832.x","type":"journal-article","created":{"date-parts":[[2007,7,5]],"date-time":"2007-07-05T12:01:40Z","timestamp":1183636900000},"page":"440-454","source":"Crossref","is-referenced-by-count":10,"title":["Genetic intratumour heterogeneity in high\u2010grade brain tumours is associated with telomere\u2010dependent mitotic instability"],"prefix":"10.1111","volume":"33","author":[{"given":"C.","family":"Glanz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Rebetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Stew\u00e9nius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Persson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Englund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Mandahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Mertens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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