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.

An update on head and neck cancer: new entities and their histopathology, molecular background, treatment, and outcome

“…A similar overlap in copy number alterations between neuroendocrine carcinoma of the salivary gland a lung has also been reported . Similarly, only few data on the mutational landscape of olfactory neuroblastoma are available with preferential affection of TP53 and a heterogeneous pattern of copy‐number alterations .…”

Pattern of loco‐regional relapses and treatment in pediatric esthesioneuroblastoma: The French very rare tumors group (Fracture) contribution

“…This observation may explain the more aggressive biological behavior of ENB during childhood and the poor survival in our series. A recent study found that half of ENBs have clinically relevant genomic alteration, which are identified in different genes such as TP53 , PIK3CA , NF1 , CDKN2A , or CDKN2C . Recently, Classe et al reported an integrative multiomics analysis of ENB identifying two subgroups of ENBs: neural and basal .…”

Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options

“…Data from several CGH studies have shown the changes that include gains at 7q, 9p, 13q, 17q, 17p13, 20p/q, 22q, and Xp/q, and losses or deletions at 1p, 2q, 3p/q, 6q, 9p, 10p/q, 22q, and Xp/q, with high‐grade ENBs demonstrating more alterations than low‐grade tumors . None of these changes have been routinely observed, limiting their prognostic or diagnostic value.…”

“…Several studies utilizing comparative genomic hybridization (CGH) have identified complex patterns of copy number abnormalities in ENB tumors, but few observations were consistent across studies , limiting generalizable conclusions and indicating that heterogeneous sets of alterations can drive ENB development. Even fewer studies have used DNA sequencing techniques to profile ENB , with three tumors in the literature evaluated by comprehensive sequencing methods . There are no mutations in ENB tumors reported in commonly used databases collating genomic cancer data, such as COSMIC, cBioPortal, and the ICGC portal.…”