title: Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment.
abstract: Olfactory neuroblastoma (ONB, Esthesioneuroblastoma) is an infrequent neoplasm of the head and neck area derived from olfactory neuroepithelium. Despite relatively good prognosis a subset of patients shows recurrence, progression and/or metastatic disease, which requires additional treatment. However, neither prognostic nor predictive factors are well specified. Thus, we performed a literature search for the currently available data on disturbances in molecular pathways, cytogenetic changes and results gained by next generation sequencing (NGS) approaches in ONB in order to gain an overview of genetic alterations which might be useful for treating patients with ONB. We present briefly ONB molecular pathogenesis and propose potential therapeutic targets and prognostic factors. Possible therapeutic targets in ONB include: receptor tyrosine kinases (c-kit, PDGFR-b, TrkB; EGFR); somatostatin receptor; FGF-FGFR1 signaling; Sonic hedgehog pathway; apoptosis-related pathways (Bcl-2, TRAIL) and neoangiogenesis (VEGF; KDR). Furthermore, we compare high- and low-grade ONB, and describe its frequent mimicker: sinonasal neuroendocrine carcinoma. ONB is often a therapeutic challenge, so our goal should be the implementation of acquired knowledge into clinical practice, especially at pretreated, recurrent and metastatic stages. Moreover, the multicenter molecular studies are needed to increase the amount of available data.
authors.affiliation: Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Czapiewski
authors.affiliation: Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Kunc
authors.affiliation: Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Haybaeck
mesh_terms: D018304:Esthesioneuroblastoma, Olfactory / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D009296:Nasal Cavity / Q000473:pathology*; D009669:Nose Neoplasms / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis
keywords: comparative genomic hybridization; esthesioneuroblastoma; mutation; next generation sequencing; olfactory neuroblastoma