Distinct MiRNA Expression Signature in Olfactory Neuroblastoma
Stefan Costinean, Veronica Balatti, Paola Dama, Luciano Cascione, Carlo M Croce, Paul E Wakely. Ohio State University, Columbus, OH
Background: Olfactory neuroblastoma (ONB) is a malignant neuroectodermal tumor that arises from neuroectodermal elements of the olfactory mucosa. Median age for this cancer is 50 years and the 5 year survival is 50 to 66%. MiRNAs have important roles in the posttranscriptional regulation of gene expression. Recently, miRNA profiling has shown that tumors and normal tissues are characterized by specific patterns of miRNA expression, so called signatures that could be used for diagnosis as well as for targeted therapy.
Design: We attempted to identify for the first time a specific miRNA signature of ONB versus normal olfactory neuroectodermal tissue. For this purpose, 5 cases of olfactory neuroblastoma, and 3 cases of normal olfactory neuroectodermal tissue were selected. RNA was analyzed using Nanostring.
Results: We identified 36 microRNAs that were differentially expressed in ONB vs normal tissue. Of 36 genes, 20 were upregulated and 16 were downregulated. 18 of the upregulated genes were expressed more than two times in ONB than in normal tissue whereas 3 of the downregulated genes were 3 times less expressed.
Conclusions: MiRNA profiling of ONB vs normal olfactory neuroectodermal tissue showed a distinct signature represented by 36 different genes that were deregulated. These genes seem to be specific to ONB and differ from the miRNAs identified as deregulated in the literature in adrenal neuroblastomas. That could be represented by a heat map with a “checkered” pattern distinct enough to allow for a specific diagnosis of these tumors.
Of 20 genes that were upregulated, a majority (17) were expressed more than twice compared to the normal control. Of the 18 downregulated genes, 8 were expressed two times less than the normal control. 3 genes were downregulated more than three times than the normal tissue. This specific microRNA signature could be useful for diagnostic purposes, when histology is not conclusive enough to allow for a clear cut diagnosis. Understanding the molecular pathways involved in this type of cancer, with a poor survival rate, will help us design targeted molecular therapies, specifically tailored for the genetic deregulation that is identified.
Category: Head & Neck
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 139, Tuesday Morning