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  1. N. T. Bleakly,
  2. M. -C. Yao*,
  3. H. Tanaka*
  1. University of Washington School of Medicine, Seattle, WA
  2. *Fred Hutchinson Cancer Research Center, Seattle, WA


The most common solid extracranial tumor that affects children is neuroblastoma. Derived from cells of the sympathetic nervous system, neuroblastoma patients older than the age of infancy have a poor prognosis. This study focuses on the tumor subset with the most unfavorable prognosis, which is characterized by genomic instability and amplification of the oncogene n-myc. Three neuroblastoma cell lines NSH, NLF, and NGP were tested for amplification of the proto-oncogene n-myc. In the cell lines where n-myc is amplified, gene expression was also tested. In addition, we then tested the n-myc-amplified cell lines for palindrome DNA sequence formation using a new microarray-based approach, genome-wide analysis of palindrome formation (GAPF). Formation of palindromes, which is initially caused by chromosome breakage, is believed to play a role in the initiation of oncogene amplification. With this microarray assay we looked for a pattern of palindrome formation that could be responsible for n-myc amplification and attempted to identify other genomic loci that may also rely on palindromic sequence formation as a means of gene amplification in neuroblastoma. Through this study, we were able to observe, define, and quantify a gene amplification phenomenon (somatic palindrome sequence formation), as well as use the assay to screen whole human genomes to further identify other loci that form somatic palindromes in neuroblastoma cell lines. The eventual hope is to identify the loci that are commonly susceptible to chromosome breakage and palindrome formation in neuroblastoma, which may uncover genotoxic stresses specific for the development of the sympathetic nervous system.

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