Large-scale analysis of chromosomal aberrations in cancer karyotypes reveals two distinct paths to aneuploidy.
Large-scale analysis of chromosomal aberrations in cancer karyotypes reveals two distinct paths to aneuploidy.
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DOI：
10.1186/gb-2011-12-6-r61
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发表时间：
2011-06-29
期刊：
影响因子：
12.3
通讯作者：
Shamir R
中科院分区：
文献类型：
--
作者：
Ozery-Flato M;Linhart C;Trakhtenbrot L;Izraeli S;Shamir R
染色体非整倍体，即染色体的获得或丢失，是癌症中最常见的异常。虽然已知某些异常，最常见的是易位，与特定的癌症密切相关，并导致它们的形成，但大多数异常似乎是非特异性的和任意的，没有明显的影响。了解染色体非整倍体及其在肿瘤发生中的作用是癌症生物学中一个基本的开放问题。我们使用Mitelman数据库中的15,000多个核型和62个癌症类别，对癌症中的染色体异常特征进行了系统的研究。值得注意的是，我们发现染色体获得与其他染色体获得的同现率很高，而丢失与丢失的同现率很高。收益和亏损很少出现显著的同时发生。这一发现在癌症类别中是一致的，并在癌症样本的独立比较基因组杂交数据集上得到证实。我们的分析结果可通过附带的网站进行进一步调查。通过对大规模数据集的统计分析，首次严格地揭示了非整倍体二分性的广泛普遍性和复杂特征，涉及许多肿瘤类别。我们的发现表明，非整倍体癌细胞可能使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，这是维持其细胞健康所必需的。
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. 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. 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.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
64.8
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DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
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20.3
作者：
Smadja, NV;Bastard, C;Fruchart, C
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Fruchart, C
了解唐氏综合症表型的基础。
影响因子：
4.5
作者：
Roper, Randall J.;Reeves, Roger H.
通讯作者：
Reeves, Roger H.