Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing.
Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing.
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DOI：
10.1038/ng.128
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发表时间：
2008-06
期刊：
影响因子：
30.8
通讯作者：
Futreal, P. Andrew
中科院分区：
文献类型：
--
作者：
Campbell, Peter J.;Stephens, Philip J.;Pleasance, Erin D.;O'Meara, Sarah;Li, Heng;Santarius, Thomas;Stebbings, Lucy A.;Leroy, Catherine;Edkins, Sarah;Hardy, Claire;Teague, Jon W.;Menzies, Andrew;Goodhead, Ian;Turner, Daniel J.;Clee, Christopher M.;Quail, Michael A.;Cox, Antony;Brown, Clive;Durbin, Richard;Hurles, Matthew E.;Edwards, Paul A. W.;Bignell, Graham R.;Stratton, Michael R.;Futreal, P. Andrew
人类癌症经常携带许多体外获得的基因组重排，其中一些可能与癌症的发展有关。但是，表征重排的传统策略是费力的，低通量，敏感性低或分辨率较差。我们使用了大量平行的测序来从两个肺癌个体的基因组得出的短DNA片段的两端产生序列读取。通过研究在参考人基因组上相互正确对齐的读对，我们表征了306个生殖线结构变体和103个躯体重排，以分辨的基础对水平。种系和躯体重排的模式明显不同。尽管在这些区域之外，特别是包括串联重复的重新排列，但许多体细胞重排来自扩增子。一些躯体重排导致异常转录本，包括内部串联重复的两个和两个由染色体重排产生的融合转录本。种系变体主要是由逆转录置置介导的，通常涉及Aluy和Line元素。结果表明，复杂的人类癌症基因组重排的系统，全基因组的表征的可行性，从而提高了使用该策略与癌症相关的新基因收获的前景。
Human cancers often carry many somatically acquired genomic rearrangements, some of which may be implicated in cancer development. However, conventional strategies for characterizing rearrangements are laborious and low-throughput and have low sensitivity or poor resolution. We used massively parallel sequencing to generate sequence reads from both ends of short DNA fragments derived from the genomes of two individuals with lung cancer. By investigating read pairs that did not align correctly with respect to each other on the reference human genome, we characterized 306 germline structural variants and 103 somatic rearrangements to the base-pair level of resolution. The patterns of germline and somatic rearrangement were markedly different. Many somatic rearrangements were from amplicons, although rearrangements outside these regions, notably including tandem duplications, were also observed. Some somatic rearrangements led to abnormal transcripts, including two from internal tandem duplications and two fusion transcripts created by interchromosomal rearrangements. Germline variants were predominantly mediated by retrotransposition, often involving AluY and LINE elements. The results demonstrate the feasibility of systematic, genome-wide characterization of rearrangements in complex human cancer genomes, raising the prospect of a new harvest of genes associated with cancer using this strategy.
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DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
56.9
作者：
Tomlins, SA;Rhodes, DR;Chinnaiyan, AM
通讯作者：
Chinnaiyan, AM
DOI：
10.1073/pnas.1232418100
发表时间：
2003-06-24
影响因子：
11.1
作者：
Volik, S;Zhao, SY;Collins, C
通讯作者：
Collins, C
影响因子：
6.4
作者：
HUPPI, K;SIWARSKI, D
通讯作者：
SIWARSKI, D
影响因子：
7
作者：
Ning, ZM;Cox, AJ;Mullikin, JC
通讯作者：
Mullikin, JC