Neuroblastoma: clinical significance of genetic abnormalities

Two genetic events have been identified so far which are characteristic of neuroblastomas. These include loss of a critical region on the distal short arm of chromosome 1 and amplification of the MYCN proto-oncogene. Our studies suggest that the two genetic events may be related and that loss of heterozygosity (LOH) for chromosome 1p may precede the development of amplification. When these features are combined with flow cytometric analysis of DNA content, three distinct genetic subsets of neuroblastomas can be identified. The first is characterized by a hyperdiploid or near-triploid modal karyotype, with few if any cytogenetic rearrangements. These patients are generally less than one year of age with localized disease and a good prognosis. The second group is characterized by a near-diploid or near-tetraploid karyotype, with no consistent rearrangement identified so far. They are generally older patients with more advance stages of disease that progress slowly and are frequently fatal. The third group is characterized by a near-diploid or tetraploid karyotype, with deletions or LOH for chromosome 1p, amplification of MYCN or both. These patients are generally older with advanced stages of disease which is rapidly progressive. Thus, genetic analysis of neuroblastoma cells provides information that has prognostic significance and can direct the choice of treatment more appropriately.