Ameloblastoma RNA profiling uncovers a distinct non-coding RNA signature
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Haleh Davanian1, Anangi Balasiddaiah1,2, Robert Heymann1,7, Magnus Sundström3, Poppy Redenström1, Mikael Silfverberg1, David Brodin4, Matti Sällberg2, Sven Lindskog5,6, Carina Kruger Weiner1,7, Margaret Chen1,2
1Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden
2Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden
3Rudbecklaboratory, Molecular Pathology Unit, Department of Pathology, Uppsala University Hospital and Department of Immunology, Genetics and Pathology, Uppsala University, Sweden
4Department of Biosciences and Nutrition, Bioinformatics and Expression Analysis SciLifeLab, Karolinska Institutet, Huddinge, Sweden
5Department of Oncology and Pathology, Karolinska Institutet, Huddinge, Sweden
6Clinical Pathology and Cytology, Karolinska University Hospital, Karolinska University Hospital, Solna, Sweden
7The Clinic of Oral and Maxillofacial Surgery, Karolinska University Hospital, Huddinge, Sweden
Margaret Chen, email: [email protected]
Keywords: ameloblastoma, biomarkers, transcriptome, ncRNA, gene expression analysis
Received: July 25, 2016 Accepted: November 30, 2016 Published: December 10, 2016
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.
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