Gains and losses of DNA sequences in childhood brain tumors analyzed by comparative genomic hybridization

Primary central nervous system neoplasms are the most common solid tumors in children. Genetic changes underlying childhood brain-tumor development and progression are incompletely characterized. To get an overview of the genetic events leading to the development of brain tumors and to identify chromosomal regions that may contain genes important in brain-tumor progression, we employed a comparative genomic hybridization technique. Twenty-four pediatric primary brain tumors were analyzed in this study. DNA copy number changes were observed in most of the samples (79%), and almost all chromosomes were involved. The total number of genetic aberrations (copy-number gains and losses per tumor) was significantly higher in the cerebellar primitive neuroectodermal tumor subgroup than in the gliomas. The high-grade tumors had more DNA changes than did the low-grade tumors. The most often gained chromosomes were: 6q (45%), 4q (34.5%), and chromosome 1 (24% of the cases). The minimal common regions involved in DNA gains were narrowed down to 6q14-16 and 4q26-28. Losses of a specific chromosome (partly or as a whole) occurred on average in 7% of the cases. Chromosomal regions that were most often lost included chromosome 1 (17%), chromosome 16 (17%), and chromosome 2 (14%). These findings suggest that genes localized to these minimal common chromosomal regions play a role in the tumorogenesis of childhood brain tumors. Our results indicate: (1) a great degree of genomic imbalance in these tumors; (2) that a high number of aberrations correlate with aggressive tumor biology; (3) and that nonrandom genetic changes may be associated with particular tumor types.