小柯机器人

首个染色体不稳定性的泛癌图谱问世
2022-06-16 19:36

近日,英国剑桥癌症研究所Florian Markowetz、Geoff Macintyre等研究人员合作绘制出染色体不稳定性的泛癌图谱。相关论文于2022年6月15日在线发表在《自然》杂志上。

研究人员评估了代表33种癌症类型的7880个肿瘤的染色体不稳定(CIN)程度、多样性和来源。研究人员提出了一个17个拷贝数特征的汇总,这些特征描述了特定类型的CIN,并有多个独立数据来源支持的潜在病因。这些特征可以预测药物反应并确定新的药物靶标。这个框架完善了对同源重组受损的理解,同源重组是CIN中最可治疗的类型之一。这些结果阐明了人类癌症基因组复杂性的基本结构,并提供了指导未来CIN研究的资源。

据介绍,CIN导致DNA大规模丢失、增加和重排的积累。CIN引起的广泛的基因组复杂性是癌症的一个标志;然而,没有一个系统的框架来衡量不同类型的CIN及其对泛癌症临床表型的影响。

附:英文原文

Title: A pan-cancer compendium of chromosomal instability

Author: Drews, Ruben M., Hernando, Barbara, Tarabichi, Maxime, Haase, Kerstin, Lesluyes, Tom, Smith, Philip S., Morrill Gavarr, Lena, Couturier, Dominique-Laurent, Liu, Lydia, Schneider, Michael, Brenton, James D., Van Loo, Peter, Macintyre, Geoff, Markowetz, Florian

Issue&Volume: 2022-06-15

Abstract: Chromosomal instability (CIN) results in the accumulation of large-scale losses, gains and rearrangements of DNA1. The broad genomic complexity caused by CIN is a hallmark of cancer2; however, there is no systematic framework to measure different types of CIN and their effect on clinical phenotypes pan-cancer. Here we evaluate the extent, diversity and origin of CIN across 7,880 tumours representing 33 cancer types. We present a compendium of 17 copy number signatures that characterize specific types of CIN, with putative aetiologies supported by multiple independent data sources. The signatures predict drug response and identify new drug targets. Our framework refines the understanding of impaired homologous recombination, which is one of the most therapeutically targetable types of CIN. Our results illuminate a fundamental structure underlying genomic complexity in human cancers and provide a resource to guide future CIN research. Copy number signatures characterize different types of chromosomal instability and predict drug response.

DOI: 10.1038/s41586-022-04789-9

Source: https://www.nature.com/articles/s41586-022-04789-9

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

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