Loss of Heterozygosity for Chromosomes 1 or 14 Defines Subsets of Advanced Neuroblastomas1

Neuroblastomas have been characterized genetically by N-mir ampli fication and by deletions or loss of heterozygosity (LOH) for the short arm of chromosome 1. However, recent studies have suggested deletion or allelic loss involving at least three other chromosome arms, llq, I4q. and 17p. Therefore, we undertook an analysis of allelic loss for these respective chromosomal arms to determine the frequency and pattern of LOH as well as the correlation of these findings with other biological and clinical variables. A group of 24 pairs of normal and tumor DNAs was chosen that were representative of patients of different ages and stages. A substantial frequency of LOH (>20%) was found only for Ip and 14q, whereas LOH for the other chromosome arms occurred in <5% of cases. On the basis of these results, we extended the analysis to a total of 59 neuroblastomas, and we found 1p LOH in 15 of the 59 cases (25%) and 1-4(| LOH in 10 of 43 informative cases (23%). N-m.ir amplification was found in 15 of the 59 cases (25%). This analysis confirmed that Ip LOH and 14q LOH occurred almost exclusively in patients with advanced stages of disease. Furthermore, LOH for Ip and 14q usually occurred independent of each other, and l p LOH frequently was associated with N-mir amplification, whereas 14q LOH was not. Thus, our results demonstrate that neuroblastomas are complex genetically and that there are at least two distinct loci for putative suppressor genes that are deleted independently in this tumor, both of which are associated with advanced