Array comparative genomic hybridization analysis of olfactory neuroblastoma

Abstract

Olfactory neuroblastoma is an unusual neuroectodermal malignancy, which is thought to arise at the olfactory membrane of the sinonasal tract. Due to its rarity, little is understood regarding its molecular and cytogenetic abnormalities. The aim of the current study is to identify specific DNA copy number changes in olfactory neuroblastoma. Thirteen dissected tissue samples were analyzed using array comparative genomic hybridization. Our results show that gene copy number profiles of olfactory neuroblastoma samples are complex. The most frequent changes included gains at 7q11.22-q21.11, 9p13.3, 13q, 20p/q, and Xp/q, and losses at 2q31.1, 2q33.3, 2q37.1, 6q16.3, 6q21.33, 6q22.1, 22q11.23, 22q12.1, and Xp/q. Gains were more frequent than losses, and high-stage tumors showed more alterations than low-stage olfactory neuroblastoma. Frequent changes in high-stage tumors were gains at 13q14.2-q14.3, 13q31.1, and 20q11.21-q11.23, and loss of Xp21.1 (in 66% of cases). Gains at 5q35, 13q, and 20q, and losses at 2q31.1, 2q33.3, and 6q16-q22, were present in 50% of cases. The identified regions of gene copy number change have been implicated in a variety of tumors, especially carcinomas. In addition, our results indicate that gains in 20q and 13q may be important in the progression of this cancer, and that these regions possibly harbor genes with functional relevance in olfactory neuroblastoma.

High Resolution Array-CGH Characterization of Human Stem Cells Using a Stem Cell Focused Microarray

“…A recent study suggests this commonly observed duplication in ESCs results in better growth, larger colonies, increased cell survival and decreased differentiation [4]. Moreover, duplication of 20q11 is frequently found in cancer [11,12]. Several genes located in this region are thought to confer a selective advantage to the cells.…”

Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

“…Another study by Guled et al with very strict morphological and immunohistochemical inclusion criteria involved 13 ONB cases [53]. Gains were more frequent than losses.…”

The role of systemic therapy in the management of sinonasal cancer: A critical review

“…Primary mucosal melanoma characteristically exerts at high frequency c-KIT overexpression, RAS-mitogen-activated protein kinase pathway alterations, CDKN2A mutations, loss of p16 expression (mainly related to 9p21deletions) and loss of heterozygosity; contrary to cutaneous melanoma, BRAF gene mutations are uncommon in mucosal counterpart [9]. In ONB a complex pattern of gene alterations were described, although no specific mutations have been reported [10]. As the most frequent tumor of the small salivary glands, adenoid cystic carcinoma shows a wide range of genetic and molecular alterations, with possible prognostic role or with potential therapeutic implications (EGFR, TrkC/NTRK3, PI3K/AKT pathway) [11].…”