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神经母细胞瘤在胎儿早期发育中产生并且其演化时间可预测结果
2023-03-30 15:40

近日,德国癌症研究中心Thomas Höfer等研究人员合作发现,神经母细胞瘤在胎儿早期发育中产生并且其演化时间可预测结果。相关论文于2023年3月27日在线发表在《自然—遗传学》杂志上。

研究人员通过深入的全基因组测序、分子钟分析和涵盖所有亚型的综合队列的群体遗传模型来量化了神经母细胞瘤的体细胞演化。研究人员发现,整个临床谱系中的肿瘤早在怀孕的前三个月就开始通过异常有丝分裂发展。预后良好的神经母细胞瘤在短暂的演化后克隆性地扩展,而侵袭性神经母细胞瘤则显示出长时间的演化,在这期间它们获得端粒维持机制。最初的非整倍体化事件制约了随后的演化,而侵袭性神经母细胞瘤表现出早期的基因组不稳定性。研究人员在发现队列(n=100)中发现,并在一个独立队列(n=86)中验证,即:演化的持续时间是一个准确的预测结果。因此,对神经母细胞瘤演化的洞察力可以前瞻性地指导治疗决策。

据了解,神经母细胞瘤是婴儿中最常见的实体瘤,并显示出非常不同的结果,从自发的消退到致命的疾病。这些不同的肿瘤起源于什么时候,以及它们是如何演变的,目前还不清楚。

附:英文原文

Title: Neuroblastoma arises in early fetal development and its evolutionary duration predicts outcome

Author: Krber, Verena, Stainczyk, Sabine A., Kurilov, Roma, Henrich, Kai-Oliver, Hero, Barbara, Brors, Benedikt, Westermann, Frank, Hfer, Thomas

Issue&Volume: 2023-03-27

Abstract: Neuroblastoma, the most frequent solid tumor in infants, shows very diverse outcomes from spontaneous regression to fatal disease. When these different tumors originate and how they evolve are not known. Here we quantify the somatic evolution of neuroblastoma by deep whole-genome sequencing, molecular clock analysis and population-genetic modeling in a comprehensive cohort covering all subtypes. We find that tumors across the entire clinical spectrum begin to develop via aberrant mitoses as early as the first trimester of pregnancy. Neuroblastomas with favorable prognosis expand clonally after short evolution, whereas aggressive neuroblastomas show prolonged evolution during which they acquire telomere maintenance mechanisms. The initial aneuploidization events condition subsequent evolution, with aggressive neuroblastoma exhibiting early genomic instability. We find in the discovery cohort (n=100), and validate in an independent cohort (n=86), that the duration of evolution is an accurate predictor of outcome. Thus, insight into neuroblastoma evolution may prospectively guide treatment decisions.

DOI: 10.1038/s41588-023-01332-y

Source: https://www.nature.com/articles/s41588-023-01332-y

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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