Chromothripsis-like patterns are recurring but heterogeneously distributed features in a survey of 22,347 cancer genome screens.
Chromothripsis-like patterns are recurring but heterogeneously distributed features in a survey of 22,347 cancer genome screens.
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DOI：
10.1186/1471-2164-15-82
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发表时间：
2014-01-29
期刊：
影响因子：
4.4
通讯作者：
Baudis M
中科院分区：
文献类型：
--
作者：
Cai H;Kumar N;Bagheri HC;von Mering C;Robinson MD;Baudis M
染色体碎裂是最近发现的一种基因组重排现象，可能在单个基因组破碎事件中出现。这可以为癌症发展提供另一种范例，用“一次性”灾难性事件取代基因组变化的逐渐积累。然而，该术语已与不同的操作定义一起使用，最小的共识是大量本地聚集的拷贝数畸变。这些类染色体碎裂模式（CTLP）的机制及其对肿瘤发生的具体影响仍然知之甚少。在这里，我们在 918 个癌症样本中鉴定出了 CTLP，这些样本来自涵盖 132 种癌症类型的 22,000 多个肿瘤基因组阵列的数据集。碎片热点被发现位于 8、11、12 和 17 号染色体上。在各种癌症类型中，软组织肿瘤的 CTLP 频率特别高。基因组背景分析表明，CTLP 重排经常发生在另外含有多个拷贝数畸变 (CNA) 的基因组中。对受影响染色体区域的调查显示，很大一部分是臂级粉碎和端粒相关事件，这与许多潜在机制兼容。我们还报告了这些基因组事件可能与患者年龄、分期和生存率相关的证据。通过对肿瘤基因组阵列数据集的大规模分析，本研究描述了与基因组畸变模式相关的特征，与之前使用的“染色体碎裂”定义的范围兼容。在量化癌症样本中聚集的基因组拷贝数畸变时，我们的数据表明这些类似染色体碎裂的模式背后存在潜在的生物异质性，超出了明确定义的“染色体碎裂”现象。
Chromothripsis is a recently discovered phenomenon of genomic rearrangement, possibly arising during a single genome-shattering event. This could provide an alternative paradigm in cancer development, replacing the gradual accumulation of genomic changes with a “one-off” catastrophic event. However, the term has been used with varying operational definitions, with the minimal consensus being a large number of locally clustered copy number aberrations. The mechanisms underlying these chromothripsis-like patterns (CTLP) and their specific impact on tumorigenesis are still poorly understood. Here, we identified CTLP in 918 cancer samples, from a dataset of more than 22,000 oncogenomic arrays covering 132 cancer types. Fragmentation hotspots were found to be located on chromosome 8, 11, 12 and 17. Among the various cancer types, soft-tissue tumors exhibited particularly high CTLP frequencies. Genomic context analysis revealed that CTLP rearrangements frequently occurred in genomes that additionally harbored multiple copy number aberrations (CNAs). An investigation into the affected chromosomal regions showed a large proportion of arm-level pulverization and telomere related events, which would be compatible to a number of underlying mechanisms. We also report evidence that these genomic events may be correlated with patient age, stage and survival rate. Through a large-scale analysis of oncogenomic array data sets, this study characterized features associated with genomic aberrations patterns, compatible to the spectrum of “chromothripsis”-definitions as previously used. While quantifying clustered genomic copy number aberrations in cancer samples, our data indicates an underlying biological heterogeneity behind these chromothripsis-like patterns, beyond a well defined “chromthripsis” phenomenon.
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影响因子：
4.5
作者：
Deakin JE;Bender HS;Pearse AM;Rens W;O'Brien PC;Ferguson-Smith MA;Cheng Y;Morris K;Taylor R;Stuart A;Belov K;Amemiya CT;Murchison EP;Papenfuss AT;Graves JA
通讯作者：
Graves JA
影响因子：
3.7
作者：
Cai H;Kumar N;Baudis M
通讯作者：
Baudis M
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3.5
作者：
Kloosterman, Wigard P.;Guryev, Victor;Cuppen, Edwin
通讯作者：
Cuppen, Edwin