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人类乳腺癌基因组中体细胞重排的复杂景观。

Complex landscapes of somatic rearrangement in human breast cancer genomes.

机构信息

Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.

出版信息

Nature. 2009 Dec 24;462(7276):1005-10. doi: 10.1038/nature08645.


DOI:10.1038/nature08645
PMID:20033038
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3398135/
Abstract

Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspective on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development.

摘要

在癌症基因组中经常发现多个体细胞重排;然而,重排的潜在过程及其对癌症发展的贡献仍未得到充分描述。在这里,我们使用配对末端测序策略来鉴定乳腺癌基因组中的体细胞重排。一些乳腺癌中的重排比以前认为的更为频繁。重排在基因足迹上更为频繁,大多数为重排是染色体内的。存在多种重排结构,但串联重复在某些癌症中特别常见,这可能反映了 DNA 维持中的特定缺陷。大多数重排连接处的短重叠序列表明这些是由非同源末端连接 DNA 修复介导的,尽管不同的序列模式表明存在多种这种类型的过程。虽然鉴定了几个表达框内融合基因,但没有一个是复发性的。该研究为癌症基因组提供了一个新的视角,突出了体细胞重排的多样性及其对癌症发展的潜在贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/c1280cfb209a/ukmss-28075-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/9e51a466832e/ukmss-28075-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/98768b0e4aac/ukmss-28075-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/213ecb835aaa/ukmss-28075-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/48a683e477da/ukmss-28075-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/91c04c8a5a3c/ukmss-28075-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/e288de6a6c02/ukmss-28075-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/c1280cfb209a/ukmss-28075-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/9e51a466832e/ukmss-28075-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/98768b0e4aac/ukmss-28075-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/213ecb835aaa/ukmss-28075-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/48a683e477da/ukmss-28075-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/91c04c8a5a3c/ukmss-28075-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/e288de6a6c02/ukmss-28075-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b16/3398135/c1280cfb209a/ukmss-28075-f0007.jpg

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Complex landscapes of somatic rearrangement in human breast cancer genomes.

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[2]
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[3]
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Phenomics. 2024-3-6

[4]
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Nat Commun. 2024-10-5

[5]
Identify Non-mutational p53 Functional Deficiency in Human Cancers.

Genomics Proteomics Bioinformatics. 2024-12-3

[6]
53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR).

bioRxiv. 2024-9-13

[7]
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Cancer Res Treat. 2025-4

[8]
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[9]
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[10]
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Cancer Immunol Res. 2024-3-4

本文引用的文献

[1]
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Nat Rev Genet. 2009-8

[2]
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Mol Cancer Ther. 2009-6

[3]
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Nature. 2009-4-9

[4]
Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas.

Cancer Res. 2008-11-1

[5]
Comprehensive genomic characterization defines human glioblastoma genes and core pathways.

Nature. 2008-10-23

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Replication licensing and cancer--a fatal entanglement?

Nat Rev Cancer. 2008-10

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Mapping short DNA sequencing reads and calling variants using mapping quality scores.

Genome Res. 2008-11

[8]
Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing.

Nat Genet. 2008-6

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The endless tale of non-homologous end-joining.

Cell Res. 2008-1

[10]
Non-homologous end-joining, a sticky affair.

Oncogene. 2007-12-10

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