Ameloblastoma RNA profiling uncovers a distinct non-coding RNA signature

// Haleh Davanian 1 , Anangi Balasiddaiah 1, 2 , Robert Heymann 1, 7 , Magnus Sundstrom 3 , Poppy Redenstrom 1 , Mikael Silfverberg 1 , David Brodin 4 , Matti Sallberg 2 , Sven Lindskog 5, 6 , Carina Kruger Weiner 1, 7 , Margaret Chen 1, 2 1 Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden 2 Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden 3 Rudbecklaboratory, Molecular Pathology Unit, Department of Pathology, Uppsala University Hospital and Department of Immunology, Genetics and Pathology, Uppsala University, Sweden 4 Department of Biosciences and Nutrition, Bioinformatics and Expression Analysis SciLifeLab, Karolinska Institutet, Huddinge, Sweden 5 Department of Oncology and Pathology, Karolinska Institutet, Huddinge, Sweden 6 Clinical Pathology and Cytology, Karolinska University Hospital, Karolinska University Hospital, Solna, Sweden 7 The Clinic of Oral and Maxillofacial Surgery, Karolinska University Hospital, Huddinge, Sweden Correspondence to: Margaret Chen, email: margaret.chen@ki.se Keywords: ameloblastoma, biomarkers, transcriptome, ncRNA, gene expression analysis Received: July 25, 2016      Accepted: November 30, 2016      Published: December 10, 2016 ABSTRACT Ameloblastoma of the jaws remains the top difficult to treat odontogenic tumour and has a high recurrence rate. New evidence suggests that non-coding RNAs (ncRNAs) play a critical role in tumourgenesis and prognosis of cancer. However, ameloblastoma ncRNA expression data is lacking. Here we present the first report of ameloblastoma ncRNA signatures. A total of 95 ameloblastoma cases and a global array transcriptome technology covering > 285.000 full-length transcripts were used in this two-step analysis. The analysis first identified in a test cohort 31 upregulated ameloblastoma-associated ncRNAs accompanied by signalling pathways of cancer, spliceosome, mRNA surveillance and Wnt. Further validation in an independent cohort points out the long non-coding (lncRNAs) and small nucleolar RNA (snoRNAs): LINC340, SNORD116-25, SNORA11, SNORA21, SNORA47 and SNORA65 as a distinct ncRNA signature of ameloblastoma. Importantly, the presence of these ncRNAs was independent of BRAF-V600E and SMO-L412F mutations, histology type or tumour location, but was positively correlated with the tumour size. Taken together, this study shows a systematic investigation of ncRNA expression of ameloblastoma, and illuminates new diagnostic and therapeutic targets for this invasive odontogenic tumour.