Specific gene expression profiles and unique chromosomal abnormalities are associated with regressing tumors among infants with disseminated neuroblastoma

Abstract

9501 Background: Among human cancers, neuroblastoma (NB) has the highest incidence of spontaneous remission, especially among the subgroup of stage 4s NB affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical, since it is the basis for therapeutic decisions. The identification of biological markers that allow a precise distinction of these NB subgroups will aid accurate classification. Methods: Thirty-seven infants with NB were treated at MSKCC from 1987 to 2000. Ten stage 4s and 19 stage 4 were evaluated by allelic and gene expression analyses. Results: All stage 4s patients underwent spontaneous remission while only 69% of newly diagnosed, previously untreated stage 4 patients survived despite combined modality therapy. Among stage 4 tumors, 19/19 were near-diploid/tetraploid, 8/19 MYCN amplified, 50% had LOH at 1p36, 43% had LOH at 1p34-p31 and/or 14q and 37% had LOH at 11q and/or 1p22. Among stage 4s tumors, 7/8 were near-triploid, none MYCN-amplified and LOH was restricted to 11q. Gene expression profiling identified 233 differentially expressed genes between stage 4 and 4s tumors. 25% of these genes with increased expression in stage 4s NB mapped to 1pter-p13, with transcription level correlated with LOH and ploidy. Conclusions: These findings suggest that differential expression of subsets of genes located at specific chromosomal regions play a significant role in the biology of disseminated NB. Besides offering a biological definition of stage 4s, these expression profiles may provide new insights in the genetic control of spontaneous remission in neuroblastoma. No significant financial relationships to disclose.