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Genetics and Genomics of Neuroblastoma

Chapter
First Online:
Part of the Cancer Treatment and Research book series (CTAR, volume 155)

Abstract

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.

Keywords

Anaplastic Lymphoma Kinase MYCN Amplification Neuroblastoma Tumor Neuroblastoma Patient TrkA Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.CEINGE Advanced Biotechnologies, University of Naples “Federico II”NaplesItaly
  2. 2.Oncology Division, Center for Childhood Cancer ResearchThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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