小柯机器人

研究揭示良性和恶性组织中空间分辨率的克隆拷贝数改变
2022-08-13 23:47

近日,瑞典皇家理工学院Joakim Lundeberg、英国牛津大学Alastair D. Lamb等研究人员合作揭示良性和恶性组织中空间分辨率的克隆拷贝数改变。该研究于2022年8月10日发表于国际一流学术期刊《自然》。

研究人员使用一种系统的方法来研究了原位的空间基因组完整性,并描述了以前未发现的克隆关系。研究人员使用空间分辨率的转录组学来推断了跨越多个器官、良性和恶性组织的>120,000个区域的空间拷贝数变化。通过以前列腺为重点的器官范围的方法,研究人员表明,全基因组拷贝数变异揭示出肿瘤内和附近的良性组织中不同的克隆模式。这些结果提出了一个模型,说明基因组不稳定性是如何在组织学上的良性组织中产生的,这可能代表了癌症进化的早期事件。研究人员强调了在组织范围内捕捉分子和空间连续性的力量,并对治疗范式(包括焦点疗法)的理由提出挑战。

据了解,定义从良性组织到恶性组织的过渡是改善癌症早期诊断的基础。

附:英文原文

Title: Spatially resolved clonal copy number alterations in benign and malignant tissue

Author: Erickson, Andrew, He, Mengxiao, Berglund, Emelie, Marklund, Maja, Mirzazadeh, Reza, Schultz, Niklas, Kvastad, Linda, Andersson, Alma, Bergenstrhle, Ludvig, Bergenstrhle, Joseph, Larsson, Ludvig, Alonso Galicia, Leire, Shamikh, Alia, Basmaci, Elisa, Daz De Sthl, Teresita, Rajakumar, Timothy, Doultsinos, Dimitrios, Thrane, Kim, Ji, Andrew L., Khavari, Paul A., Tarish, Firaz, Tanoglidi, Anna, Maaskola, Jonas, Colling, Richard, Mirtti, Tuomas, Hamdy, Freddie C., Woodcock, Dan J., Helleday, Thomas, Mills, Ian G., Lamb, Alastair D., Lundeberg, Joakim

Issue&Volume: 2022-08-10

Abstract: Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.

DOI: 10.1038/s41586-022-05023-2

Source: https://www.nature.com/articles/s41586-022-05023-2

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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