Allelic deletion at 11q23 is common in MYCN single copy neuroblastomas

Deletions of the long arm of chromosome 11 (11q) have been noted in primary neuroblastomas, but a comprehensive analysis has not been performed. There fore, we analysed 331 neuroblastomas (295 sporadic, 15 familial and 21 tumo r-derived cell Lines) to determine the prevalence of 11q allelic deletions, to map the location of a putative tumor suppressor gene and to perform cli nical correlative studies. Assays for loss of heterozygosity (LOH) were per formed at 24 microsatellite loci spanning 11q, LOH was observed at multiple 11q loci in 129/295 (44%) sporadic neuroblastomas, 5/15 (33%) familial neu roblastomas, and 5/21 (24%) neuroblastoma cell lines. A single region of 2. 1 cM within 11q23,3, flanked by markers D11S1340 and D11S1299, was deleted in all specimens with 11q LOH, Allelic loss at 11q23 was inversely related to MYCN amplification (P < 0,001), Within the subset of cases with a single copy of MYCN 11q LOH was associated with advanced stage disease (P = 0,008 ), unfavorable histopathology (P = 0,042), and decreased overall survival p robability (P = 0,008), However, 11q LOH was not independently prognostic i n multivariate analyses, These data support the hypothesis that a tumor sup pressor gene mapping within 11q23,3 is commonly inactivated during the mali gnant evolution of a large subset of neuroblastomas, especially those with unamplified MYCN.