Allelic status on 1p and 11p15 in neuroblastoma and benign ganglioneuroma

A tumor suppressor gene responsible for neuroblastoma (NB) is thought to be located on 1p, while a gene(s) commonly involved in embryonal tumors in childhood is(are) located on 11p15. To determine whether and how those putative genes affect tumorigenesis of NB, a total of 25 NBs and two benign ganglioneuromas (GNs) were examined by Southern technique with polymorphic markers on chromosomes 1 and 11 for analysis of the loss of heterozygosity at these loci. Because NB often features an increased number of chromosomes, we performed a detailed examination of allelic status and then compared it with their prognostic factors. While allelic loss on 1p was observed in only four cases (16%), eight additional cases showed allelic imbalance on a portion of 1p, indicating that these cases featured 1p deletions, so that the total number of cases with a 1p deletion was 12 out of 25 NBs (48%). A 1p deletion was observed not only in disseminated cases (8/14 of stage III or TV), but also in several cases with localized tumors (4/11 of stage I or II, p=0.529). Moreover, one GN case showed a 1p deletion. However, allelic loss or imbalance on 11p15 was observed in only two NBs (8%). These data suggest that 1p deletion is an initial event of NE tumorigenesis rather than a later event associated with tumor progression, while deletion of 11p15 is related to the development of a small proportion of NBs. Cases with 1p deletion do not always follow an aggressive clinical course and may differentiate into GN.