The neuroblastoma and ganglion components of nodular ganglioneuroblastoma are genetically similar: evidence against separate clonal origins

Abstract

Nodular ganglioneuroblastoma is characterized by a macroscopic nodule of neuroblastoma within a ganglioneuromatous component. These two components have been considered to originate from separate clones, with the neuroblastoma clone accounting for the clinical behavior of nodular ganglioneuroblastoma. In order to investigate the clonal origin of the cellular components (neuroblasts, ganglion cells, and Schwann cells) of nodular ganglioneuroblastoma, paraffin-embedded tumor samples from eight cases were analyzed by single nucleotide polymorphism array and in situ hybridization. DNA was extracted separately from neuroblastomatous and ganglioneuromatous areas. By in situ hybridization, MYCN gain (4-10 gene copies/ nucleus) was detected in 7/8 neuroblastoma samples. In ganglioneuromatous regions, gains were also detected in ganglion cells but not in Schwann cells. Single-nucleotide polymorphism array studies identified chromosome losses (11q and 14q) and gains (12, 13q, 17q and 18q) in the neuroblastoma component, whereas the ganglioneuromatous component showed fewer or no genetic alterations. There were no unique copy number changes distinguishing nodular ganglioneuroblastoma from other subtypes of neuroblastoma. By in situ hybridization, ganglion cells but not Schwann cells showed the same alterations detected in neuroblasts. Thus, neuroblasts and ganglion cells in nodular ganglioneuroblastoma are genetically related and may arise from the same clone. In contrast, the Schwann cells have a different origin and may be derived from a nonneoplastic neural crest precursor. Our results suggest that the clinical behavior of nodular ganglioneuroblastoma cannot be explained by the presence of separate clones with distinct genetic signatures.

Adult‐onset neuroblastoma: Report of seven cases with molecular genetic characterization

“…FISH analysis for MYCN copy number, chromosome 1p loss and chromosome 17q gain was performed as previously described . Briefly, spectrum orange‐ or spectrum green‐labeled bacterial artificial chromosomes (BACs) DNA were acquired from the Applied Centre for Genomics, Toronto, Canada (http://www.tcag.ca/) and selected based on the UCSC genome browser (http://genome.ucsc.edu).…”

11q deletion in neuroblastoma: a review of biological and clinical implications

“…When tested, 11q loss was also detected in the ganglioneuromatous component of the tumour, but not in Schwann cells. Altogether, the results obtained from using SNP arrays and FISH suggest that Schwann cells have a different origin and are not clonally related to the other compounds [133]. …”

Development and validation of a prognostic nomogram for patients with ganglioneuroblastoma: A SEER-based study

“…Andrew et al reported that the 5-year survival probability of patients with GNB was approximately 88 % and that the prognosis of children with GNB was better than that of adolescents and adults with GNB [ 8 ]. In a survival analysis of 232 GNB patients, Paola Angelini et al reported that age was an independent prognostic risk factor for GNB [ 7 ]. Many studies have revealed that ageing increases the risk of cancer, which is possibly related to the accumulation of gene mutations throughout the life cycle [ 21 , 22 ].…”

“…GNB primarily affects children – its incidence rate in this population is no more than 5 cases per million children – but it can also occur in adolescents and adults [ 5 ]. Age is an independent prognostic factor for GNB [ 6 , 7 ]. A retrospective study suggested that the 5-year survival rate of GNB patients was approximately 88 % [ 8 ].…”