Genetics and Genomics of Neuroblastoma
Genetics and Genomics of Neuroblastoma
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DOI：
10.1007/978-1-4419-6033-7_4
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Diskin, Sharon J.
中科院分区：
文献类型：
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作者：
Capasso, Mario;Diskin, Sharon J.
神经母细胞瘤是一种发生在儿童交感神经系统的癌症。它仍然是一个重要的儿科问题，因为它约占儿童癌症死亡率的15%。该疾病在临床上是异质性的，治愈的可能性根据诊断时的年龄、疾病的程度和肿瘤生物学而变化很大。这种极端的临床异质性反映了与疾病发展和进展相关的遗传和基因组事件的复杂性。已在神经母细胞瘤中鉴定了启动肿瘤发生的遗传性遗传变异和突变，并描述了与疾病进展相关的多种体细胞获得性基因组改变。本章重点介绍了最近的全基因组研究，这些研究利用高密度单核苷酸多态性（SNP）基因分型阵列来发现诱发肿瘤发生的遗传因素，如2p23位点的罕见突变（在ALK基因中）对于家族性神经母细胞瘤，常见SNP位于6p22（FLJ22536和FLJ44180）和2q35（BARD1）的拷贝数多态性，以及散发性神经母细胞瘤1q21.1（NBPF 23）的拷贝数多态性。它还涉及众所周知的和最近报道的肿瘤基因组的体细胞变化，如突变，等位基因的获得和癌基因的激活，等位基因的丢失，或肿瘤细胞倍性的变化，导致神经母细胞瘤的不同临床行为。最后，本章回顾了神经母细胞瘤的基因表达谱与神经营养因子和凋亡因子的信号转导途径，可能有一个在神经母细胞瘤的发展和进展的作用。展望未来，一个主要的挑战将是了解肿瘤基因组中遗传的遗传变异和获得性体细胞改变如何与神经母细胞瘤和一般癌症的确切表型差异相互作用。
Neuroblastoma is a pediatric cancer of the developing sympathetic nervous system that most often affects young children. It remains an important pediatric problem because it accounts for approximately 15% of childhood cancer mortality. The disease is clinically heterogeneous, with the likelihood of cure varying greatly according to age at diagnosis, extent of disease, and tumor biology. This extreme clinical heterogeneity reflects the complexity of genetic and genomic events associated with development and progression of disease. Inherited genetic variants and mutations that initiate tumorigenesis have been identified in neuroblastoma and multiple somatically acquired genomic alterations have been described that are relevant to disease progression. This chapter focuses on recent genome-wide studies that have utilized high-density single nucleotide polymorphism (SNP) genotyping arrays to discover genetic factors predisposing to tumor initiation such as rare mutations at locus 2p23 (in ALK gene) for familial neuroblastoma, common SNPs at 6p22 (FLJ22536 and FLJ44180) and 2q35 (BARD1), and a copy number polymorphism at 1q21.1 (NBPF23) for sporadic neuroblastoma. It also deals with well known and recently reported somatic changes in the tumor genome such as mutations, gain of alleles and activation of oncogenes, loss of alleles, or changes in tumor-cell ploidy leading to the diverse clinical behavior of neuroblastomas. Finally, this chapter reviews gene expression profiles of neuroblastoma associated with pathways of the signaling of neurotrophins and apoptotic factors that could have a role in neuroblastoma development and progression. Looking forward, a major challenge will be to understand how inherited genetic variation and acquired somatic alterations in the tumor genome interact to exact phenotypic differences in neuroblastoma, and cancer in general.