LOSS OF HETEROZYGOSITY FOR CHROMOSOME-1 OR CHROMOSOME-14 DEFINES SUBSETS OF ADVANCED NEUROBLASTOMAS

Neuroblastomas have been characterized genetically by N-myc amplificat ion and by deletions or loss of heterozygosity (LOH) for the short arm of chromosome 1. However, recent studies have suggested deletion or a llelic loss involving at least three other chromosome arms, 11q, 14q, 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 biologica l 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 (greater-than-or-equal-to 20%) was found only for 1p and 14q, whereas LOH for the other chromosome a rms occurred in less-than-or-equal-to 5% of cases. On the basis of the se results, we extended the analysis to a total of 59 neuroblastomas, and we found 1p LOH in 15 of the 59 cases (25%) and 14q LOH in 10 of 4 3 informative cases (23%). N-myc amplification was found in 15 of the 59 cases (25%). This analysis confirmed that 1p LOH and 14q LOH occurr ed almost exclusively in patients with advanced stages of disease. Fur thermore, LOH for 1p and 14q usually occurred independent of each othe r, and 1p LOH frequently was associated with N-myc amplification, wher eas 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 stages of disease.