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上皮性卵巢癌中存在大量的中心体缺陷。

A catalog of numerical centrosome defects in epithelial ovarian cancers.

机构信息

Biology of Centrosomes and Genetic Instability, Institut Curie, PSL Research University, CNRS UMR 144, Paris, France.

Department of Translational Research, Institut Curie, PSL University, Paris Cedex 05, France.

出版信息

EMBO Mol Med. 2022 Sep 7;14(9):e15670. doi: 10.15252/emmm.202215670.

DOI:10.15252/emmm.202215670
PMID:36069081
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9449595/
Abstract

Centrosome amplification, the presence of more than two centrosomes in a cell is a common feature of most human cancer cell lines. However, little is known about centrosome numbers in human cancers and whether amplification or other numerical aberrations are frequently present. To address this question, we have analyzed a large cohort of primary human epithelial ovarian cancers (EOCs) from 100 patients. We found that rigorous quantitation of centrosome number in tumor samples was extremely challenging due to tumor heterogeneity and extensive tissue disorganization. Interestingly, even if centrosome clusters could be identified, the incidence of centrosome amplification was not comparable to what has been described in cultured cancer cells. Surprisingly, centrosome loss events where a few or many nuclei were not associated with centrosomes were clearly noticed and overall more frequent than centrosome amplification. Our findings highlight the difficulty of characterizing centrosome numbers in human tumors, while revealing a novel paradigm of centrosome number defects in EOCs.

摘要

中心体扩增,即一个细胞中存在两个以上的中心体,是大多数人类癌细胞系的一个常见特征。然而,关于人类癌症中的中心体数量以及扩增或其他数值异常是否经常存在,人们知之甚少。为了解决这个问题,我们分析了来自 100 名患者的大量原发性人上皮性卵巢癌 (EOC) 肿瘤样本。我们发现,由于肿瘤异质性和组织广泛紊乱,对肿瘤样本中中心体数量进行严格定量是极具挑战性的。有趣的是,即使可以识别中心体簇,中心体扩增的发生率也无法与在培养的癌细胞中所描述的相媲美。令人惊讶的是,中心体丢失事件,即少数或许多细胞核与中心体没有关联,明显被注意到,并且比中心体扩增更为常见。我们的研究结果强调了在人类肿瘤中描述中心体数量的困难,同时揭示了 EOC 中中心体数量缺陷的新范例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e47/9449595/42a822208051/EMMM-14-e15670-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e47/9449595/6a8f1aa5dd78/EMMM-14-e15670-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e47/9449595/f0aaa4e41b68/EMMM-14-e15670-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e47/9449595/ecf160369f58/EMMM-14-e15670-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e47/9449595/42a822208051/EMMM-14-e15670-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e47/9449595/6a8f1aa5dd78/EMMM-14-e15670-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e47/9449595/f0aaa4e41b68/EMMM-14-e15670-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e47/9449595/ecf160369f58/EMMM-14-e15670-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e47/9449595/42a822208051/EMMM-14-e15670-g005.jpg

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Differences in Mitotic Spindle Architecture in Mammalian Neural Stem Cells Influence Mitotic Accuracy during Brain Development.哺乳动物神经干细胞有丝分裂纺锤体结构的差异影响大脑发育过程中的有丝分裂准确性。
Curr Biol. 2019 Sep 23;29(18):2993-3005.e9. doi: 10.1016/j.cub.2019.07.061. Epub 2019 Sep 5.
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Centrosome loss results in an unstable genome and malignant prostate tumors.
M phase-specific generation of supernumerary centrioles in cancer cells.
癌细胞中M期特异性产生的多余中心粒。
Mol Biol Cell. 2025 Jun 1;36(6):ar65. doi: 10.1091/mbc.E24-08-0386. Epub 2025 Apr 23.
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Amplified centrosomes-more than just a threat.扩增的中心体——不仅仅是威胁。
EMBO Rep. 2024 Oct;25(10):4153-4167. doi: 10.1038/s44319-024-00260-0. Epub 2024 Sep 16.
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