Signatures of mutation and selection in the cancer genome.
Signatures of mutation and selection in the cancer genome.
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作者：
癌症基因组由体细胞突变和选择的双重过程塑造。癌症基因组中的纯合缺失发生在隐性癌基因上，它们可以赋予选择性的生长优势，并且比脆弱的部位，在那里它们被认为反映了DNA破裂的局部局部速率。然而，癌症基因组中的大多数纯合缺失是无法解释的。在这里，我们确定了746个癌细胞系中的2,428个体纯合缺失。因此，这些覆盖了11％的蛋白质编码基因，因此并不是人类细胞存活的强制性。我们得出了结构性特征，这些标志区分了隐性癌基因和脆弱部位的纯合缺失。应用于无法解释的纯合缺失群，表明许多属于固有的脆弱性区域，而一个小的子集叠加隐性癌基因。结果说明了如何使用结构特征来区分癌症基因组突变和选择的影响。可用于此大量公开可用的癌细胞系的广泛拷贝数，基因分型，序列和表达数据为癌症生物学和药物发现的未来研究提供了丰富的试剂。
The cancer genome is moulded by the dual processes of somatic mutation and selection. Homozygous deletions in cancer genomes occur over recessive cancer genes, where they can confer selective growth advantage, and over fragile sites, where they are thought to reflect an increased local rate of DNA breakage. However, most homozygous deletions in cancer genomes are unexplained. Here we identified 2,428 somatic homozygous deletions in 746 cancer cell lines. These overlie 11% of protein-coding genes that, therefore, are not mandatory for survival of human cells. We derived structural signatures that distinguish between homozygous deletions over recessive cancer genes and fragile sites. Application to clusters of unexplained homozygous deletions suggests that many are in regions of inherent fragility, whereas a small subset overlies recessive cancer genes. The results illustrate how structural signatures can be used to distinguish between the influences of mutation and selection in cancer genomes. The extensive copy number, genotyping, sequence and expression data available for this large series of publicly available cancer cell lines renders them informative reagents for future studies of cancer biology and drug discovery.
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影响因子：
64.5
作者：
Casper, AM;Nghiem, P;Glover, TW
通讯作者：
Glover, TW
影响因子：
3.5
作者：
Ried, K;Finnis, M;Richards, RI
通讯作者：
Richards, RI
影响因子：
64.8
作者：
Liu, Man;Duke, Jamie L.;Schatz, David G.
通讯作者：
Schatz, David G.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
7
作者：
Perry, George H.;Yang, Fengtang;Redon, Richard
通讯作者：
Redon, Richard