Multiple Genes with Potential Tumor Suppressive Activity Are Present on Chromosome 10q Loss in Neuroblastoma and Are Associated with Poor Prognosis

SIMPLE SUMMARY: Specific recurrent segmental aberrations (SCA) have been associated with poor survival in neuroblastoma (NB). The effect of many other not recurrent SCA has not been clarified yet. Here we examined the role of the loss of chromosome 10q in a cohort of 260 NB primary tumors, observing a lower survival rate for the patients expressing this rare SCA. We identified a cluster of 75 genes in the long arm of chromosome 10, whose deletion was associated with poorer survival. Six genes, and in particular CCSER2, appeared to be good candidates to play a role as tumor suppressor genes in NB and possible targets for future therapeutic interventions. ABSTRACT: Neuroblastoma (NB) is a tumor affecting the peripheral sympathetic nervous system that substantially contributes to childhood cancer mortality. Despite recent advances in understanding the complexity of NB, the mechanisms determining its progression are still largely unknown. Some recurrent segmental chromosome aberrations (SCA) have been associated with poor survival. However, the prognostic role of most SCA has not yet been investigated. We examined a cohort of 260 NB primary tumors at disease onset for the loss of chromosome 10q, by array-comparative genomic hybridization (a-CGH) and Single Nucleotide Polymorphism (SNP) array and we found that 26 showed 10q loss, while the others 234 displayed different SCA. We observed a lower event-free survival for NB patients displaying 10q loss compared to patients with tumors carrying other SCA. Furthermore, analyzing the region of 10q loss, we identified a cluster of 75 deleted genes associated with poorer outcome. Low expression of six of these genes, above all CCSER2, was significantly correlated to worse survival using in silico data from 786 NB patients. These potential tumor suppressor genes can be partly responsible for the poor prognosis of NB patients with 10q loss.