英国伦敦大学学院癌症研究所Nischalan Pillay和加州大学圣地亚哥分校Ludmil B. Alexandrov共同合作，近期取得重要工作进展。他们研究发现了人类癌症中拷贝数改变的特征。 相关工作2022年6月15日在线发表于《自然》杂志上。
在这里，研究人员提出了一个概念框架来鉴定人类癌症中拷贝数改变的模式，该框架广泛适用于多种数据类型，包括全基因组测序、全外显子组测序、亚硫酸氢盐测序、单细胞DNA测序和SNP6微阵列数据。将该框架部署到来自癌症基因组图谱6中的代表33种人类癌症类型的9,873种癌症中，揭示了一组21个拷贝数特征，这些特征解释了97%样本的拷贝数模式。17个拷贝数特征归结为全基因组加倍、非整倍性、杂合性丧失、同源重组缺陷、染色体碎裂和单倍体化的生物学现象。四个拷贝数特征的病因仍未得到解释。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增益相关的扩增子特征，例如MDM2。与基础规模的突变特征相比，没有拷贝数特征与许多已知的外源性癌症风险因素关。
他们的研究结果通过揭示导致这些改变的多种突变过程，综合了人类癌症拷贝数改变的全球格局。
据介绍，DNA的获得和丢失在癌症中普遍存在，是复制应激、有丝分裂错误、纺锤体多极和断裂- 融合-桥循环等相互关联过程的结果，这些过程可能导致染色体不稳定和非整倍性产生。这些拷贝数的改变有助于癌症的起始、进展和治疗耐药性产生。
附：英文原文
Title: Signatures of copy number alterations in human cancer
Author: Steele, Christopher D., Abbasi, Ammal, Islam, S. M. Ashiqul, Bowes, Amy L., Khandekar, Azhar, Haase, Kerstin, Hames-Fathi, Shadi, Ajayi, Dolapo, Verfaillie, Annelien, Dhami, Pawan, McLatchie, Alex, Lechner, Matt, Light, Nicholas, Shlien, Adam, Malkin, David, Feber, Andrew, Proszek, Paula, Lesluyes, Tom, Mertens, Fredrik, Flanagan, Adrienne M., Tarabichi, Maxime, Van Loo, Peter, Alexandrov, Ludmil B., Pillay, Nischalan
Issue&Volume: 2022-06-15
Abstract: 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 aneuploidy1,2. These copy number alterations contribute to cancer initiation, progression and therapeutic resistance3,4,5. 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 Atlas6 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.
DOI: 10.1038/s41586-022-04738-6
Source: https://www.nature.com/articles/s41586-022-04738-6
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
