Copy number loss accounted for most of the regions of LOH and was found on chromosomes, in which genes on the retained alleles are thought to be haplo in sufficient or inactivated by intrachromosomal deletions, mutations, or epigenetic phenomena. LOH with a normal copy number was documented in all 4 of the tumors with LOH on chromosome 11p. Such LOH without accompanying copy number reduction, termed ����copy-neutral���� events have been reported in rhabdomyosarcoma, breast cancer, and acute myeloid leukemia, and are thought to be due to uniparental disomy, which result in the loss of one allele and duplication of the retained allele. The fact that in 3 tumors the regions of 11p LOH extended to the telomere suggests that this phenomenon is likely due to somatic recombination. In tumor #427, entire chromosome 11 LOH is seen, suggesting either a somatic recombination event close to the centromere or a nondisjunction event with subsequent chromosomal duplication. This may result in gain of function of the genes in this region, as for example, IGF2, which is known to induce neuroblastoma cell proliferation. Alternatively, the targeted gene within this region on the duplicated allele may also contain inactivating mutations or be suppressed by epigenetic mechanisms, resulting in loss of function. Further studies are required to determine which gene or genes are mutated and how the mutations that led to their inactivation were selected for in the first place. We also observed LOH accompanied by an increase in copy number on chromosome 17q. The loss of one allele followed by a gain of the remaining allele would suggest the need to eliminate the wild-type function of an activated oncogene. This phenomenon has been suggested previously in osteosarcomas, where LOH was accompanied by a significant increase in copy number. Alternatively, copy number gain and the resulting allelic imbalance may result in a false reading of LOH by the genotyping algorithm. Indeed, all three of our samples with MYCN amplification on chromosome 2p24 appeared to have LOH at that locus.