文章：

神经母细胞瘤：临床谜题的生物学见解

Neuroblastoma: biological insights into a clinical enigma

原文发布日期：2003-03-01

DOI: 10.1038/nrc1014

类型: Review Article

开放获取: 否

要点：

1. Neuroblastoma is the most common extracranial tumour of childhood. This tumour originates from precursor cells of the peripheral (sympathetic) nervous system and usually arises in a paraspinal location in the abdomen or chest.
2. The aetiology of neuroblastoma is unknown, but it seems unlikely that environmental exposures are important. A subset of patients inherits a genetic predisposition to neuroblastoma, and these patients usually have multifocal primary tumours that arise at an early age. A predisposition locus has been mapped to the short arm of chromosome 16.
3. Neuroblastomas can be classified into subtypes that are predictive of clinical behaviour based on the patterns of genetic change. This information can be useful in the selection of therapy.
4. Favourable tumours are characterized by near-triploid karyotypes with whole chromosome gains. These tumours rarely have structural rearrangements, and they usually express the TrkA neurotrophin receptor. Patients with these tumours are more likely to be less than 1 year of age, have localized tumours and a good prognosis.
5. Unfavourable tumours are characterized by structural changes, including deletions of 1p or 11q, unbalanced gain of 17q and/or amplification of the MYCN protooncogene. They might also express the TrkB neurotrophin receptor and its ligand, brain-derived neurotrophic factor (BDNF). These patients are usually older than 1 year of age, have more advanced stages of disease and a much worse prognosis, even with aggressive treatment.
6. Mass screening for neuroblastoma at 6–12 months of age led to an increased prevalence of neuroblastoma detected in the screened populations, but no decrease in mortality from this disease. The tumours detected have overwhelmingly been of the favourable genetic subtype.
7. Novel, biologically based therapies are being developed that would specifically target the genes, proteins and pathways that are responsible for malignant transformation and progression in neuroblastomas. These approaches are likely to be more effective and less toxic than conventional therapy.
8. In the future, it is likely that more extensive molecular profiling of the genetic changes and expression patterns of neuroblastoma will lead to an even more precise subclassification system that will be predictive of outcome, as well as therapies to which the tumour is most likely to be responsive.

要点翻译：

1. 神经母细胞瘤是儿童期最常见的颅外肿瘤。这种肿瘤起源于外周（交感）神经系统的前体细胞，通常发生于腹部或胸部的脊柱旁区域。
2. 神经母细胞瘤的病因尚不明确，但环境暴露因素似乎不太可能是主要诱因。部分患者继承了神经母细胞瘤的遗传易感性，这些患者通常发病年龄较早，且表现为多灶性原发性肿瘤。一个易感基因位点已被定位在16号染色体的短臂。
3. 根据遗传改变的模式，神经母细胞瘤可被分为不同的亚型，这些亚型能够预测临床行为。这一信息对于治疗方案的选择具有指导意义。
4. 预后良好型肿瘤的特征表现为近三倍体核型伴全染色体增加。这类肿瘤很少出现结构重排，通常表达TrkA神经营养因子受体。患有此类肿瘤的患者多为1岁以下婴幼儿，肿瘤多为局限性，预后良好。
5. 预后不良型肿瘤的特征表现为结构改变，包括1p或11q缺失、17q不平衡增加和/或MYCN原癌基因扩增。它们可能还表达TrkB神经营养因子受体及其配体脑源性神经营养因子（BDNF）。这类患者通常年龄大于1岁，疾病分期更晚，即使接受积极治疗预后也较差。
6. 对6-12月龄婴儿进行神经母细胞瘤大规模筛查，虽然提高了筛查人群中该病的检出率，但并未降低其死亡率。被检出的肿瘤绝大多数属于遗传亚型中的预后良好型。
7. 目前正在研发基于生物学的新型疗法，旨在特异性靶向导致神经母细胞瘤恶性转化和进展的基因、蛋白及信号通路。这些方法可能比传统疗法更有效且毒性更低。
8. 未来，更广泛的分子谱分析技术对神经母细胞瘤遗传改变和表达模式的解析，很可能催生出能更精准预测预后的亚分类系统，并指导选择肿瘤最可能响应的治疗方案。

英文摘要：

Neuroblastoma is a tumour derived from primitive cells of the sympathetic nervous system and is the most common solid tumour in childhood. Interestingly, most infants experience complete regression of their disease with minimal therapy, even with metastatic disease. However, older patients frequently have metastatic disease that grows relentlessly, despite even the most intensive multimodality therapy. Recent advances in understanding the biology and genetics of neuroblastomas have allowed classification into low-, intermediate- and high-risk groups. This allows the most appropriate intensity of therapy to be selected — from observation alone to aggressive, multimodality therapy. Future therapies will focus increasingly on the genes and biological pathways that contribute to malignant transformation or progression.

摘要翻译： 

神经母细胞瘤是起源于交感神经系统原始细胞的肿瘤，是儿童最常见的实体瘤。有趣的是，大多数婴儿即使已发生转移，仅需极少的干预即可完全缓解。然而，年长患儿常表现为持续进展的转移性疾病，即使接受最强烈的多模式治疗仍难以控制。近年来，对神经母细胞瘤生物学和遗传学的深入认识使其可被划分为低、中、高危组，从而选择最恰当的治疗强度——从单纯观察到积极的多模式治疗。未来的治疗将更加聚焦于参与恶性转化或进展的基因和生物学通路。

原文链接：

Neuroblastoma: biological insights into a clinical enigma