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No Evidence for the Presence of an Imprinted Neuroblastoma Suppressor Gene within Chromosome Sub-Band 1p36.3¹

Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4318 [M. D. H., C. L. W., X. L., C. G., P. S. W., G. M. B., J. M. M.]; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 [M. D. H., P. S. W., G. M. B., J. M. M.]; and Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115 [A. T. L.]

Deletion of the distal short arm of chromosome 1 occurs in 35% of primary neuroblastomas (NBs). These deletions tend to be large and extend to the telomere, but a common region within sub-band 1p36.3 is consistently lost. Despite intensive investigation, no candidate tumor suppressor gene within this region has been shown to undergo tumor-specific mutation consistent with biallelic inactivation. In addition, initial studies demonstrated preferential loss of the maternally inherited 1p homologue in NBs with 1p loss of heterozygosity (LOH) without MYCN amplification. This has led to the widely accepted hypothesis that a genomically imprinted NB suppressor gene is the target of 1p deletion in this subset. To test this hypothesis we have studied 293 primary NBs for LOH within 1p36.3 and determined the parental origin of the deleted 1p homologue. LOH within 1p36.3 was demonstrated in 55 NBs (19%). Of these, 29 occurred in tumors without MYCN amplification: 13 had deletion of the maternally inherited 1p, whereas 16 had deletion of the paternally inherited 1p (P = 0.58). These data strongly refute a parent-of-origin effect for 1p deletions in NB and exclude the existence of an imprinted NB suppressor locus in this region.

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