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  • 发现罕见儿童癌症的起源可以指导治疗

    时间: 2021年2月22日  浏览:94次  来自:盛诺一家 返回上页

    “这是我们第一次能够证明双侧神经母细胞瘤肿瘤可以是独立的实体。对于每个病人来说,临床医生能够区分正在扩散的侵袭性肿瘤和一组局部的良性肿瘤是非常重要的。如果肿瘤没有转移,我们可以考虑减少强化治疗,减少副作用。”

    新的研究表明,患者体内的双侧神经母细胞瘤可以彼此独立地发生。这类肿瘤尚未从一个部位扩散(转移)到另一个部位,这一发现对理解神经母细胞瘤的根源具有重要意义,并可能促进更好的治疗。

    来自Wellcome Sanger研究所、剑桥大学、剑桥大学医院、大奥蒙德街儿童医院和伦敦大学学院大奥蒙德街儿童健康研究所的研究人员研究了两名患者多个部位的肿瘤基因组。在这两个病例里,患者体内的肿瘤都是独立发生的,它们的起源都是在胚胎发育阶段。发表在今天(11月4日)的《新英格兰医学杂志》上的研究结果可能与治疗其它类型的双侧肿瘤有关。

    神经母细胞瘤是一种高度侵袭性的儿童癌症。在英国,每年大约有100名儿童受到影响。它是由胎儿在子宫发育过程中遗留下来的特化神经细胞——成神经细胞发展而来的。

    神经母细胞瘤最常见于肾脏上方的一个肾上腺。神经母细胞瘤有几种不同的类型,有些更具侵袭性。在罕见的病例中会发生双侧肿瘤,例如在双侧肾上腺中。

    与物种的进化相似,人体内的单个细胞在成长过程中也会受到变异和选择的影响。这些“体细胞突变”在细胞分裂时从一个细胞传递到另一个细胞。在一生中,不同的突变会在不同细胞的DNA中积累。通过比较肿瘤细胞和健康细胞之间的体细胞突变模式,就有可能追踪它们的进化历史。

    在这项新的研究中,Wellcome Sanger研究所的研究人员对双侧神经母细胞瘤进行了广泛的基因组测序。进化基因组学表明,个体的神经母细胞瘤肿瘤是在生命的最早期阶段独立受精后出现的。研究中的两个孩子都遗传了一种使他们容易患癌症的基因突变。


    “由于测序技术的进步和分析方法的发展,最近将儿童癌症的起源追溯到胚胎已经成为可能。这是我们对肿瘤的看法以及它们在成为肿瘤之前如何相互联系的范式转变。独立肿瘤的平行进化是一个意想不到的有趣发现,它揭示了神经母细胞瘤的起源于受精卵的最初几次分裂。”

    ——Wellcome Sanger研究所的Tim Coorens,该研究的第一作者


    了解病人体内的肿瘤是否独立是临床医生在决定最佳治疗方案时的重要信息。通常认为多发部位的肿瘤是从原发肿瘤扩散而来的转移性疾病。与保留在组织微环境中的肿瘤相比,已经从一个部位转移并扩散到另一个部位的肿瘤更具侵略性,并且需要更多的强化治疗。


    “这是我们第一次能够证明双侧神经母细胞瘤肿瘤可以是独立的实体。对于每个病人来说,临床医生能够区分正在扩散的侵袭性肿瘤和一组局部的良性肿瘤是非常重要的。如果肿瘤没有转移,我们可以考虑减少强化治疗,减少副作用。”

    ——John Anderson,敦大学学院大奥蒙德街儿童健康研究所和大奥蒙德街儿童医院教授,该研究论文的作者。


    研究人员猜测其它类型的双侧肿瘤可能也有类似的发展模式,因此他们的发现对于分析和治疗这类癌症具有更广泛的重要意义。

    “神经母细胞瘤是最常见的儿童肿瘤之一,英国每年约有100名儿童被诊断为神经母细胞瘤。然而,它的存活率也是最低的——在高风险的情况下,存活率只有50%左右。”

    “我们欢迎这些发现,因为这是朝着开发针对神经母细胞瘤患儿更友好、更安全、更个性化的治疗迈出的重要一步,这将有助于减少当前积极治疗的长期且通常会限制生命的副作用。”

    ——Dr. Jasmine Parkinson,英国儿童癌症研究与赠款经理


    “我们现在所处的世界中,肿瘤基因组测序是医疗保健的一部分。它正在成为临床上治疗儿童癌症的重要工具。利用基因组学分析肿瘤的起源可以使我们对正在处理的疾病以及如何解决它有更深入的了解。”

    ——Dr. Sam Behjati,论文的主要作者


    Uncovering the origin of rare childhood cancer guides treatment 

    4 November 2020

    Bilateral neuroblastoma cancers in a patient can arise independently from each other, at the very earliest stages of life

    New research shows that bilateral neuroblastoma cancers within a patient can arise independently from each other. The finding that such tumours have not spread – metastasised – from one site to another has important implications for understanding the roots of neuroblastoma and may promote better treatments.

    Researchers from the Wellcome Sanger Institute, the University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Great Ormond Street Hospital for Children NHS Trust and the UCL Great Ormond Street Institute of Child Health studied the genomes of tumours from multiple sites in two patients with the condition. In both cases the tumours within a patient arose separately from each other, with their origins in embryonic development. Their findings, published in the New England Journal of Medicine today, 4th November, may be relevant for treating other types of bilateral tumours.

    Neuroblastoma is a highly aggressive childhood cancer. About 100 children each year in the UK are affected. It develops from specialised nerve cells – neuroblasts – left behind from a baby’s development in the womb*.

    Neuroblastoma most commonly occurs in one of the adrenal glands above the kidneys. There are several different types of neuroblastoma, with some more aggressive than others. In rare cases, bilateral tumours occur, for example in both adrenal glands.

    Similarly to the evolution of species, individual cells in the body are subject to forces of mutation and selection as they grow. These ‘somatic mutations’ are passed from one cell to another as it divides**. Over a lifetime, different mutations accumulate in the DNA of different cells. By comparing the patterns of somatic mutations between tumour cells and healthy cells, it is possible to trace their evolutionary history.

    In this new study, researchers at the Wellcome Sanger Institute extensively sequenced the genomes of bilateral neuroblastoma. Evolutionary genomics showed that the neuroblastoma tumours in an individual arose independently at the very earliest stages of life, within a few cell divisions after fertilization. Both children in the study had inherited a genetic mutation that predisposed them to cancer.

    “Thanks to advances in sequencing technologies and developments in analysis methods, it has recently become possible to trace the origin of childhood cancer right back to the embryo. It’s a paradigm shift in how we think about tumours, and how they are related to each other before they became tumours. The parallel evolution of independent tumours was an unexpected and fascinating finding, which reveals the very origin of neuroblastoma within the first few divisions of the fertilised egg.”

    Tim Coorens,first author of the study from the Wellcome Sanger Institute

    Understanding if tumours within a patient are independent or not is vital information for clinicians when deciding the best treatment options. It is usually assumed that tumours at multiple sites are metastatic disease that spread from an original primary tumour. A tumour that has metastasised and spread from one site to another is more aggressive – and requires more intensive treatment – than one that remains within a tissue microenvironment.

    “This is the first time we’ve been able to prove that bilateral neuroblastoma tumours can be independent entities. It is essential for each patient that clinicians can make the distinction between an aggressive tumour that is spreading, and a set of more benign tumours that are localised. If tumours haven’t metastasised, we can consider less intensive treatments, with fewer side effects.”

    Professor John Anderson,senior author of the study from the UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children NHS Foundation Trust

    The researchers suspect that other types of bilateral tumours may also have similar patterns of development, and so their findings are important more widely for analysing and treating such cancers.

    “Neuroblastoma is one of the most common childhood tumours with around 100 children diagnosed in the UK each year. Yet, it also has one of the lowest survival rates – in its high-risk form, the survival rate is sadly around just 50 per cent.

    “We welcome these findings as an important step towards the development of kinder, safer, and more personalised, treatments for children with neuroblastoma which will help reduce the long-term, and often life-limiting, side effects of current aggressive treatments.”

    Dr Jasmine Parkinson,Children with Cancer UK Research and Grants Manager

    “We are in a world now where genome sequencing tumours is a part of healthcare. It is becoming an important tool in the clinic for treating childhood cancers. Using genomics to analyse a tumour’s origins can give us detailed insight into what we are dealing with and how to tackle it.”

    Dr Sam Behjati,lead author of the study from the Wellcome Sanger Institute and Addenbrooke’s Hospital, Cambridge


    本文编译自UCL大奥蒙德街儿童健康研究所官网于2020年11月4日发表的《发现罕见儿童癌症的起源可以指导治疗》,Uncovering the origin of rare childhood cancer guides treatment ,from: https://www.ucl.ac.uk/child-health/news/2020/nov/uncovering-origin-rare-childhood-cancer-guides-treatment 


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