Abstract 5408: RNA fusion detection in thyroid nodules with a targeted RNA sequencing panel

Thyroid nodules are quite common and detected in as high as 67% of the population. Only a small portion of thyroid nodules are malignant thyroid cancers. Advances in understanding the molecular pathology of thyroid cancer are leading to the development of better biomarkers and novel targeted therapies. The tumorigenic role of RNA fusions has been reported in many forms of cancer. Fusions can result from structural rearrangements like translocations and deletions, transcription read-through of neighboring genes, or the trans- and cis-splicing of pre-mRNAs. Many fusions act as key drivers for cancer development. Detection of fusion RNA is a challenge with traditional technologies like FISH and qPCR, as they are laborious, low throughput, and do not provide detailed information about the fusion. Here we explored the possible use of a tumor fusion-targeted RNA-based panel (QIAseq targeted RNAscan panel, which is targeting 223 fusion gene pairs, 576 unique fusions) as a tool to study fusions in thyroid nodules. The presence of these fusions were surveyed in RNA samples from 10 thyroid cancer (PTC and FVPTC) samples and 19 non-cancer control samples (NH and FA) using this oncology targeted panel and sequenced on the Illumina NextSeq. PAX8-PPARG, a fusion gene with a well-established link to thyroid cancer, was found in the cancer group. In addition, we observed a universal expression of a recurrent read-through transcript, HALC1-COQL, in all thyroid nodules. Our results suggest that a targeted RNA-based panel provided a useful tool for fusion gene study in thyroid cancer. The role of the expected rearrangement and the unexpected read-through fusion in thyroid nodules needs to be further evaluated, as it could provide useful information for thyroid nodule differentiation. Citation Format: Song Tian, Michelle Baird, Frank Reinecke, Jixin Deng, Mohammad Nezami Ranjbar, Raed Samara, Eric Lader. RNA fusion detection in thyroid nodules with a targeted RNA sequencing panel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5408. doi:10.1158/1538-7445.AM2017-5408