Identification of a new lncRNA, COMET, in papillary thyroid carcinoma. COMET

Cancer Genome Atlas Consortium has identified a peculiar signature of protein-coding genes in specific papillary thyroid carcinoma subgroups. However, the expression of long non-coding RNAs (lncRNAs) has not yet been systematically measured. In addition, their correlation with specific tumor-driving mutations or rearrangements has not been assessed. Starting from the re-analysis of our RNA-Sequencing data, we used de novo discovery approach to define tumor subtype-specific signatures for annotated lncRNAs and to identify new ones. Among them, a Natural Antisense Transcript, that we named COMET (COrrelated-to-MET), was identified as a lncRNA highly expressed in carcinomas harboring BRAFV600E mutation or RET gene rearrangements (i.e. BRAF-like tumors) and induced downstream Mitogen-Activated Protein Kinase (MAPK) pathway.

癌症基因组图谱联盟（Cancer Genome Atlas Consortium）已在特定甲状腺乳头状癌亚组中鉴定出蛋白编码基因的独特特征谱。然而，长链非编码RNA（long non-coding RNAs，lncRNAs）的表达尚未得到系统性检测，且其与特定肿瘤驱动突变或基因重排的关联也未被评估。本研究从重新分析我们的RNA测序（RNA-Sequencing）数据入手，采用从头发现方法，为已注释的lncRNAs定义肿瘤亚型特异性特征谱，并鉴定出全新的lncRNAs。其中，一款被命名为COMET（COrrelated-to-MET）的天然反义转录本（Natural Antisense Transcript），在携带BRAFV600E突变或RET基因重排的癌组织（即BRAF样肿瘤）中呈高表达，且其表达受丝裂原活化蛋白激酶（Mitogen-Activated Protein Kinase，MAPK）通路下游调控诱导。