Our review confirmed that the survival of infants with stage D(S) NB is excellent. However, subsets of patients with poor prognosis can be identified by young age and unfavorable biologic factors. More effective therapy is needed for the group of stage D(S) infants who show unfavorable clinical and biologic features.

To assess the utility of fluorescence in situ hybridization (FISH) for analysis of MYCN gene amplification in neuroblastoma, we compared this assay with Southern blot analysis using tumor specimens collected from 232 patients with presenting characteristics typical of this disease. The FISH technique identified MYCN amplification in 47 cases, compared with 39 by Southern blotting, thus increasing the total number of positive cases by 21%. The major cause of discordancy was a low fraction of tumor cells (< or =30% replacement) in clinical specimens, which prevented an accurate estimate of MYCN copy number by Southern blotting. With FISH, by contrast, it was possible to analyze multiple interphase nuclei of tumor cells, regardless of the proportion of normal peripheral blood, bone marrow, or stromal cells in clinical samples. Thus, FISH could be performed accurately with very small numbers of tumor cells from touch preparations of needle biopsies. Moreover, this procedure allowed us to discern the heterogeneous pattern of MYCN amplification that is characteristic of neuroblastoma. We conclude that FISH improves the detection of MYCN gene amplification in childhood neuroblastomas in a clinical setting, thus facilitating therapeutic decisions based on the presence or absence of this prognostically important biologic marker.

Malignant rhabdoid tumors (MRT) are rare; thus very few cytogenetic studies of this type of tumor have been performed. We report the results of cytogenetic studies of 10 MRTs from various anatomic primary sites. Six cases had normal diploid karyotypes with no detectable rearrangements or aneuploidy except for occasional tetraploid cells. In 4 of these cases the tumor phenotype was verified by electron microscopic studies. In a seventh case only normal cells were identified in short-term culture, but a del(13)(q14) appeared after 4 months in culture. A soft tissue MRT contained a translocation, t(8;15)(q12;p11), and a liver MRT contained a del(3)(q21) or t(3;?)(q21;?). The single case of a primary brain MRT had monosomy 22 with deletion of part of the remaining chromosome 22. Our findings indicate that visible chromosomal rearrangements occur in fewer than half of MRTs. When combined with other reported series, our study indicates that monosomy 22 is a non-random chromosomal abnormality in primary MRT of the brain.

The majority of Ewing sarcomas and peripheral neuroectodermal tumors (PNET) that have been karyotyped contain a specific translocation, t(11;22)(q23;q11). We report here a second nonrandom translocation, der( 16)t(1; 16)(q21;q13), in 2 of 20 cases of Ewing sarcoma (seven previously unreported) and 2 of 7 cases of PNET (all previously unreported). All cases with this translocation also contained the t(l 1;22). Comparison of C-banding patterns in tumor and peripheral lymphocyte karyotypes in one case indicated that the likely breakpoints were lq21 and 16q13. The presence of this translocation in cell lines will enable further investigation of the molecular events important in the pathogenesis of Ewing sarcoma and PNET.

In three cases of alveolar rhabdomyosarcoma with variant translocations, two tumors contained an identical translocation, t(1;13)(p36.1;q14); the third tumor contained a t(8;13)(p21;q14). All three patients were 2 years old, markedly younger than the median age for patients with t(2;13)-positive alveolar rhabdomyosarcoma. The alteration of genetic material on chromosome 13 may be of primary importance in the development of alveolar rhabdomyosarcoma.