Gain of chromosome arm 17q is associated with unfavourable prognosis in neuroblastoma, but does not involve mutations in the somatostatin receptor 2 (SSTR2) gene at 17q24

Deletion of chromosome arm Ip and amplification of the MYCN oncogene are we ll-recognized genetic alterations in neuroblastoma cells. Recently, another alteration has been reported; gain of the distal part of chromosome arm 17 q, In this study 48 neuroblastoma tumours were successfully analysed for 17 q status in relation to known genetic alterations. Chromosome 17 status was detected by fluorescence in situ hybridization (FISH). Thirty-one of the 4 8 neuroblastomas (65%) showed 17q gain, and this was significantly associat ed with poor prognosis. As previously reported, 17q gain was significantly associated with metastatic stage 4 neuroblastoma and more frequently detect ed than both deletion of chromosome arm 1p and MYCN amplification in tumour s of all stages. 17q gain also showed a strong correlation to survival prob ability (P = 0.0009), However, the most significant correlation between 17q gain and survival probability was observed in children with low-stage tumo urs (stage 1, 2, 3 and 4S), with a survival probability of 100% at 5 years from diagnosis for children with tumours showing no 17q gain compared to 52 .5% for those showing 17q gain (P = 0.0021), This suggests that 17q gain as a prognostic factor plays a more crucial role in low-stage tumours. Expres sion of the somatostatin receptor 2 (SSTR2), localized in chromosome region 17q24, has in previous studies been shown to be positively related to surv ival in neuroblastoma. A point mutation in the SSTR2 gene has earlier been reported in a human small-cell lung cancer. In this study, mutation screeni ng of the SSTR2 gene in 43 neuroblastoma tumours was carried out with polym erase chain reaction-based single-stranded conformation polymorphism/hetero duplex (SSCP/HD) and DNA sequencing, and none of the tumours showed any abe rrations in the SSTR2 gene. These data suggest that mutations in the SSTR2 gene are uncommon in neuroblastoma tumours and do not correlate with either the 17q gain often seen or the reason some tumours do not express SSTR2 re ceptors. Overall, this study indicates that gain of chromosome arm 17q is t he most frequently occurring genetic alteration, and that it is associated with established prognostic factors. (C) 1999 Cancer Research Campaign.