OLFACTORY NEUROBLASTOMA IS A PERIPHERAL PRIMITIVE NEUROECTODERMAL TUMOR-RELATED TO EWING SARCOMA

Olfactory neuroblastoma (ONE) is a malignant tumor of the nasal mucosa whose histogenesis is unclear, A relationship to neuroblastoma (NB), a pediatric tumor of the sympathetic nervous system, is based on morph ologic similarities and the expression of similar neural antigens, How ever, the clinical presentation of ONE differs from that of NE, and MY CN amplification characteristic of NE is not observed, We have therefo re examined the relationship of this malignancy to other classes of ne ural tumors, In previous studies, two ONE cell lines demonstrated cyto genetic features and patterns of protooncogene expression suggestive o f a relationship to the Ewing sarcoma family of childhood peripheral p rimitive neuroectodermal tumors (pPNETs), The pPNETs show t(11;22)(q24 ;q12) or t(21;22)(q22;q12) chromosomal translocations fusing the EWS g ene from 22q12 with either the FLII gene on 11q24 or the ERG gene on 2 1q22, We therefore analyzed ONBs for the presence of pPNET-associated gene fusions, Both cell lines showed rearrangement of the EWS gene, an d fluorescence in situ hybridization (FISH) of each case demonstrated fusion of EWS and FLII genomic sequences. Moreover, both lines express ed EWS/FLII fusion transcripts with in-frame junctions between exon 7 of EWS and exon 6 of FLII as described for pPNETs, We identified simil ar gene fusions in four of six primary ONE cases, None of the cases ex pressed tyrosine hydroxylase, a catecholamine biosynthetic enzyme wide ly expressed in NE. Our studies indicate that ONB is not a NE but is a member of the pPNET family.