Signatures of copy number alterations in human cancer.
Signatures of copy number alterations in human cancer.
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DOI：
10.1038/s41586-022-04738-6
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发表时间：
2022-06
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
--
作者：
DNA的获得和丢失在癌症中是普遍的，并且作为复制应激、有丝分裂错误、纺锤体多极和断裂-融合-桥循环等的相互关联的过程的结果而出现，这可能导致染色体不稳定性和非整倍性。这些拷贝数改变有助于癌症的发生、进展和治疗抗性。在这里，我们提出了一个概念框架，以检查拷贝数改变的模式，在人类癌症，广泛适用于不同的数据类型，包括全基因组测序，全外显子组测序，减少代表性亚硫酸氢盐测序，单细胞DNA测序和SNP 6微阵列数据。将该框架部署到来自癌症基因组图谱的代表33种人类癌症类型的9，873种癌症中，揭示了一组21个拷贝数签名，可以解释97%样本的拷贝数模式。17个拷贝数的签名归因于全基因组加倍，非整倍性，杂合性丢失，同源重组缺陷，染色体断裂和单倍体化的生物学现象。四个拷贝数签名的病因仍然无法解释。一些癌症类型具有与染色体外DNA、疾病特异性存活和原癌基因获得（如MDM 2）相关的扩增子特征。与碱基突变特征相反，没有拷贝数特征与许多已知的外源性癌症风险因素相关。我们的研究结果通过揭示引起这些改变的突变过程的多样性，综合了人类癌症中拷贝数改变的全球景观。一个新的框架，使泛癌症的参考集的拷贝数签名来自不同的实验测定等位基因特异性配置文件。
Gains and losses of DNA are prevalent in cancer and emerge as a consequence of inter-related processes of replication stress, mitotic errors, spindle multipolarity and breakage–fusion–bridge cycles, among others, which may lead to chromosomal instability and aneuploidy. These copy number alterations contribute to cancer initiation, progression and therapeutic resistance. Here we present a conceptual framework to examine the patterns of copy number alterations in human cancer that is widely applicable to diverse data types, including whole-genome sequencing, whole-exome sequencing, reduced representation bisulfite sequencing, single-cell DNA sequencing and SNP6 microarray data. Deploying this framework to 9,873 cancers representing 33 human cancer types from The Cancer Genome Atlas revealed a set of 21 copy number signatures that explain the copy number patterns of 97% of samples. Seventeen copy number signatures were attributed to biological phenomena of whole-genome doubling, aneuploidy, loss of heterozygosity, homologous recombination deficiency, chromothripsis and haploidization. The aetiologies of four copy number signatures remain unexplained. Some cancer types harbour amplicon signatures associated with extrachromosomal DNA, disease-specific survival and proto-oncogene gains such as MDM2. In contrast to base-scale mutational signatures, no copy number signature was associated with many known exogenous cancer risk factors. Our results synthesize the global landscape of copy number alterations in human cancer by revealing a diversity of mutational processes that give rise to these alterations. A new framework enables a pan-cancer reference set of copy number signatures derived from allele-specific profiles from different experimental assays.
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影响因子：
64.8
作者：
Burrell RA;McClelland SE;Endesfelder D;Groth P;Weller MC;Shaikh N;Domingo E;Kanu N;Dewhurst SM;Gronroos E;Chew SK;Rowan AJ;Schenk A;Sheffer M;Howell M;Kschischo M;Behrens A;Helleday T;Bartek J;Tomlinson IP;Swanton C
通讯作者：
Swanton C
实现癌症基因组数据的共同愿景。
DOI：
10.1056/nejmp1607591
发表时间：
2016-09-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Grossman RL;Heath AP;Ferretti V;Varmus HE;Lowy DR;Kibbe WA;Staudt LM
通讯作者：
Staudt LM
影响因子：
64.5
作者：
Davoli T;Xu AW;Mengwasser KE;Sack LM;Yoon JC;Park PJ;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.6
作者：
Behjati S;Tarpey PS;Haase K;Ye H;Young MD;Alexandrov LB;Farndon SJ;Collord G;Wedge DC;Martincorena I;Cooke SL;Davies H;Mifsud W;Lidgren M;Martin S;Latimer C;Maddison M;Butler AP;Teague JW;Pillay N;Shlien A;McDermott U;Futreal PA;Baumhoer D;Zaikova O;Bjerkehagen B;Myklebost O;Amary MF;Tirabosco R;Van Loo P;Stratton MR;Flanagan AM;Campbell PJ
通讯作者：
Campbell PJ