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大规模分析癌症核型中的染色体畸变揭示了两种不同的非整倍体途径。

Large-scale analysis of chromosomal aberrations in cancer karyotypes reveals two distinct paths to aneuploidy.

机构信息

The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.

出版信息

Genome Biol. 2011 Jun 29;12(6):R61. doi: 10.1186/gb-2011-12-6-r61.


DOI:10.1186/gb-2011-12-6-r61
PMID:21714908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3218849/
Abstract

BACKGROUND: Chromosomal aneuploidy, that is to say the gain or loss of chromosomes, is the most common abnormality in cancer. While certain aberrations, most commonly translocations, are known to be strongly associated with specific cancers and contribute to their formation, most aberrations appear to be non-specific and arbitrary, and do not have a clear effect. The understanding of chromosomal aneuploidy and its role in tumorigenesis is a fundamental open problem in cancer biology. RESULTS: We report on a systematic study of the characteristics of chromosomal aberrations in cancers, using over 15,000 karyotypes and 62 cancer classes in the Mitelman Database. Remarkably, we discovered a very high co-occurrence rate of chromosome gains with other chromosome gains, and of losses with losses. Gains and losses rarely show significant co-occurrence. This finding was consistent across cancer classes and was confirmed on an independent comparative genomic hybridization dataset of cancer samples. The results of our analysis are available for further investigation via an accompanying website. CONCLUSIONS: The broad generality and the intricate characteristics of the dichotomy of aneuploidy, ranging across numerous tumor classes, are revealed here rigorously for the first time using statistical analyses of large-scale datasets. Our finding suggests that aneuploid cancer cells may use extra chromosome gain or loss events to restore a balance in their altered protein ratios, needed for maintaining their cellular fitness.

摘要

背景:染色体非整倍性,即染色体的获得或丢失,是癌症中最常见的异常。虽然某些异常,最常见的是易位,与特定的癌症密切相关,并有助于其形成,但大多数异常似乎是非特异性和任意的,没有明显的作用。对染色体非整倍性及其在肿瘤发生中的作用的理解是癌症生物学中的一个基本开放性问题。

结果:我们使用 Mitelman 数据库中的超过 15000 个核型和 62 个癌症类别,对癌症中染色体异常的特征进行了系统研究。值得注意的是,我们发现染色体获得与其他染色体获得之间,以及染色体丢失与丢失之间存在非常高的共发生率。增益和损耗很少显示出显著的共发生。这一发现跨癌症类别一致,并在癌症样本的独立比较基因组杂交数据集上得到了证实。通过附带的网站,可以进一步研究我们分析的结果。

结论:广泛的普遍性和非整倍体二分法的复杂特征,跨越了许多肿瘤类别,这里首次通过对大规模数据集的统计分析,严格地揭示出来。我们的发现表明,非整倍体癌细胞可能利用额外的染色体获得或丢失事件来恢复其改变的蛋白质比例的平衡,这是维持其细胞适应性所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4990/3218849/ff6c67ea68bd/gb-2011-12-6-r61-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4990/3218849/657dbe84bee1/gb-2011-12-6-r61-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4990/3218849/abf33eb9a4d1/gb-2011-12-6-r61-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4990/3218849/ff6c67ea68bd/gb-2011-12-6-r61-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4990/3218849/657dbe84bee1/gb-2011-12-6-r61-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4990/3218849/abf33eb9a4d1/gb-2011-12-6-r61-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4990/3218849/ff6c67ea68bd/gb-2011-12-6-r61-3.jpg

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[9]
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本文引用的文献

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