Massive genomic rearrangement acquired in a single catastrophic event during cancer development.
Massive genomic rearrangement acquired in a single catastrophic event during cancer development.
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DOI：
10.1016/j.cell.2010.11.055
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发表时间：
2011-01-07
期刊：
影响因子：
64.5
通讯作者：
Campbell PJ
中科院分区：
文献类型：
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作者：
Stephens PJ;Greenman CD;Fu B;Yang F;Bignell GR;Mudie LJ;Pleasance ED;Lau KW;Beare D;Stebbings LA;McLaren S;Lin ML;McBride DJ;Varela I;Nik-Zainal S;Leroy C;Jia M;Menzies A;Butler AP;Teague JW;Quail MA;Burton J;Swerdlow H;Carter NP;Morsberger LA;Iacobuzio-Donahue C;Follows GA;Green AR;Flanagan AM;Stratton MR;Futreal PA;Campbell PJ
癌症是由体细胞获得的点突变和染色体重排驱动的，通常认为这些点突变和染色体重排会随着时间的推移逐渐积累。使用下一代测序，我们描述了一种现象，我们称之为chromothripsis，即在一次性细胞危机中发生数十到数百次基因组重排。涉及一个或几个染色体的重排在相关区域来回交叉，在两个拷贝数状态之间产生频繁的振荡。如果重排随着时间的推移而积累，那么这些基因组特征是极不可能的，相反，这意味着几乎所有的重排都发生在单一的细胞灾难中。在所有癌症的至少2%-3%中可以看到chromothripsis的印记，跨越许多亚型，并且存在于约25%的骨癌中。我们发现，一个，甚至不止一个，致癌病变可以从基因组危机中出现。这种现象对基因组重塑的起源和癌症的暂时出现具有重要意义。2%-3%的癌症显示出定位于特定基因组区域的10-100个重排。基因组特征意味着染色体断裂发生在一次性危机（“染色体断裂”）中。在所有肿瘤类型中发现，特别是在骨癌中常见（高达25%）。
Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%–3% of all cancers, across many subtypes, and is present in ∼25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. ► 2%–3% cancers show 10–100 s of rearrangements localized to specific genomic regions ► Genomic features imply chromosome breaks occur in one-off crisis (“chromothripsis”) ► Found across all tumor types, especially common in bone cancers (up to 25%) ► Can generate several genomic lesions with potential to drive cancer in single event
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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
作者：
通讯作者：
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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
作者：
通讯作者：
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影响因子：
64.8
作者：
通讯作者：
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