文章：

神经母细胞瘤：发育生物学、癌症基因组学和免疫治疗

Neuroblastoma: developmental biology, cancer genomics and immunotherapy

原文发布日期：2013-05-24

DOI: 10.1038/nrc3526

类型: Review Article

开放获取: 否

要点：

1. Neuroblastoma is a heterogeneous disease. Over 60% of neuroblastomas are metastatic, and most are diagnosed after 18 months of age, with a substantial number carrying MYCN amplification or α-thalassaemia/mental retardation syndrome X-linked (ATRX) mutation, and/or anaplastic lymphoma receptor tyrosine kinase (ALK) mutation. The rest have fairly few somatic mutations and are highly curable with either surgery alone or surgery and low-dose chemotherapy. Neural crest cells and neuroblastoma share common pathways and genes, including paired-like homeobox 2b (PHOX2B), MYCN and ALK.
2. A predictive profile of genetic predisposition to neuroblastoma is emerging via genome-wide association and whole-genome sequencing analyses. However, in contrast to adult cancers, there is a general paucity of recurrent somatic mutations in neuroblastoma.
3. The biology of catecholamine transport has been successfully exploited to provide the tumour-specific neurotransmitter analogue meta-iodobenzylguanidine (MIBG) for diagnosis and anti-neuroblastoma therapy. This advance shows how understanding unique tumour physiology can lead to new therapeutics that are not directly related to specific genetic lesions.
4. Chromosomal aberration is common in neuroblastoma; numerical whole-chromosomal gains are typically found in low-risk tumours, whereas segmental chromosomal gains or losses and somatic mutations are associated with high-risk disease.
5. Research on epigenetic regulation and microRNA control may uncover new prognostic markers and therapeutic targets for neuroblastoma.
6. Neuroblastoma can evade T cells and natural killer cells while exploiting inflammatory macrophages to enhance its survival. Monoclonal antibodies, cytokines and multifunctional antibodies could potentially reactivate antitumour activity in these cells.
7. Anti-GD2 antibodies, when combined with granulocyte–macrophage colony-stimulating factor with or without interleukin-2, are one of the most successful and important strategies for the curative approach to neuroblastoma. Both myeloid effectors and natural killer cells and their cell-surface activating or inhibitory receptors have crucial roles in the clinical response.

要点翻译：

1. 神经母细胞瘤是一种异质性疾病。超过60%的神经母细胞瘤发生转移，多数在18月龄后确诊，其中相当部分病例携带MYCN扩增或α-地中海贫血/智力低下综合征X连锁（ATRX）基因突变，和/或间变性淋巴瘤受体酪氨酸激酶（ALK）突变。其余病例体细胞突变较少，仅通过手术或联合低剂量化疗即可实现高治愈率。神经嵴细胞与神经母细胞瘤共享多种通路和基因，包括配对样同源框2b（PHOX2B）、MYCN及ALK基因。
2. 通过全基因组关联研究和全基因组测序分析，神经母细胞瘤遗传易感性的预测谱正在逐步显现。然而与成人癌症相反，神经母细胞瘤普遍缺乏复发性体细胞突变。
3. 儿茶酚胺转运的生物学机制已被成功应用于肿瘤特异性神经递质类似物间碘苄胍（MIBG）的研发，用于诊断及抗神经母细胞瘤治疗。这一进展表明，理解独特的肿瘤生理学可催生与特定遗传损伤不直接相关的新型疗法。
4. 染色体畸变在神经母细胞瘤中较为常见：低风险肿瘤通常出现全染色体数目增加，而节段性染色体增益/缺失及体细胞突变则与高风险疾病相关。
5. 表观遗传调控和microRNA控制的研究可能揭示神经母细胞瘤新的预后标志物和治疗靶点。
6. 神经母细胞瘤能逃逸T细胞和自然杀伤细胞的杀伤，同时利用炎症巨噬细胞增强其生存能力。单克隆抗体、细胞因子及多功能抗体或可重新激活这些细胞的抗肿瘤活性。
7. 抗GD2抗体联合粒细胞-巨噬细胞集落刺激因子（含或不含白细胞介素-2）是神经母细胞瘤治愈性方案中最成功且重要的策略之一。髓系效应细胞、自然杀伤细胞及其表面激活/抑制受体在临床应答中均发挥着关键作用。

英文摘要：

Neuroblastoma is a solid tumour that arises from the developing sympathetic nervous system. Over the past decade, our understanding of this disease has advanced tremendously. The future challenge is to apply the knowledge gained to developing risk-based therapies and, ultimately, improving outcome. In this Review we discuss the key discoveries in the developmental biology, molecular genetics and immunology of neuroblastoma, as well as new translational tools for bringing these promising scientific advances into the clinic.

摘要翻译： 

神经母细胞瘤是一种起源于发育中的交感神经系统的实体肿瘤。过去十年间，我们对这一疾病的理解取得了巨大进展。未来的挑战在于将所获知识应用于制定基于风险的治疗策略，并最终改善预后。在本综述中，我们回顾了神经母细胞瘤在发育生物学、分子遗传学和免疫学方面的关键发现，并介绍了将这些有前景的科学进展转化为临床应用的新工具。

原文链接：

Neuroblastoma: developmental biology, cancer genomics and immunotherapy