The topography of mutational processes in breast cancer genomes.
The topography of mutational processes in breast cancer genomes.
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DOI：
10.1038/ncomms11383
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发表时间：
2016-05-02
影响因子：
16.6
通讯作者：
Nik-Zainal, Serena
中科院分区：
文献类型：
--
作者：
Morganella, Sandro;Alexandrov, Ludmil B.;Glodzik, Dominik;Zou, Xueqing;Davies, Helen;Staaf, Johan;Sieuwerts, Anieta M.;Brinkman, Arie B.;Martin, Sancha;Ramakrishna, Manasa;Butler, Adam;Kim, Hyung-Yong;Borg, Ake;Sotiriou, Christos;Futreal, P. Andrew;Campbell, Peter J.;Span, Paul N.;Van Laere, Steven;Lakhani, Sunil R.;Eyfjord, Jorunn E.;Thompson, Alastair M.;Stunnenberg, Hendrik G.;de Vijver, Marc J. van;Martens, John W. M.;Borresen-Dale, Anne-Lise;Richardson, Andrea L.;Kong, Gu;Thomas, Gilles;Sale, Julian;Rada, Cristina;Stratton, Michael R.;Birney, Ewan;Nik-Zainal, Serena
人类癌症中的体细胞突变显示出与基因组结构和功能相关的基因组分布的不均匀性。然而，这些突变是通过受精卵和癌细胞之间的细胞谱系操作的多个突变过程产生的，每个突变过程由特定的DNA损伤和修复成分组成，并在基因组上留下自己的特征性突变特征。使用来自560个乳腺癌全基因组序列的体细胞突变目录，在这里，我们显示了乳腺组织中存在的12个碱基取代，2个插入/缺失（indel）和6个重排突变签名中的每一个，与转录，DNA复制和染色质组织相关的基因组特征表现出不同的关系。这种基于特征的方法允许可视化与APOBEC酶、错配修复缺陷和同源重组修复缺陷相关的突变过程的基因组分布，以及未知病因的突变过程。此外，它突出了机制的见解，包括一个假定的复制依赖性机制的APOBEC相关的诱变。 突变特征提供了给定诱变剂的作用机制的证据，并且在癌细胞中发现。在这里，使用560个乳腺癌基因组，作者证明突变特征通常与基因组结构相关，包括核小体定位和复制时间。
Somatic mutations in human cancers show unevenness in genomic distribution that correlate with aspects of genome structure and function. These mutations are, however, generated by multiple mutational processes operating through the cellular lineage between the fertilized egg and the cancer cell, each composed of specific DNA damage and repair components and leaving its own characteristic mutational signature on the genome. Using somatic mutation catalogues from 560 breast cancer whole-genome sequences, here we show that each of 12 base substitution, 2 insertion/deletion (indel) and 6 rearrangement mutational signatures present in breast tissue, exhibit distinct relationships with genomic features relating to transcription, DNA replication and chromatin organization. This signature-based approach permits visualization of the genomic distribution of mutational processes associated with APOBEC enzymes, mismatch repair deficiency and homologous recombinational repair deficiency, as well as mutational processes of unknown aetiology. Furthermore, it highlights mechanistic insights including a putative replication-dependent mechanism of APOBEC-related mutagenesis. Mutational signatures provide evidence of the mechanism of action of a given mutagen and are found in cancer cells. Here, using 560 breast cancer genomes, the authors demonstrate that mutational signatures are frequently associated with genomic architecture including nucleosome positioning and replication timing.
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影响因子：
16.6
作者：
通讯作者：
--
影响因子：
4.3
作者：
Guilbaud G;Rappailles A;Baker A;Chen CL;Arneodo A;Goldar A;d'Aubenton-Carafa Y;Thermes C;Audit B;Hyrien O
通讯作者：
Hyrien O
影响因子：
16
作者：
Harris, RS;Petersen-Mahrt, SK;Neuberger, MS
通讯作者：
Neuberger, MS
影响因子：
46.9
作者：
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影响因子：
11.4
作者：
Arcangioli, B;de Lahondès, R
通讯作者：
de Lahondès, R