Targeted next generation sequencing identifies somatic mutations and gene fusions in papillary thyroid carcinoma

// Zheming Lu 1, * , Yujie Zhang 2, * , Dongdong Feng 2 , Jindong Sheng 2 , Wenjun Yang 1, 3 and Baoguo Liu 2 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Laboratory of Biochemistry and Molecular Biology, Beijing, China 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Head and Neck Surgery, Peking University Cancer Hospital & Institute, Beijing, China 3 Key Laboratory of Fertility Preservation and Maintenance (Ministry of Education), Cancer Institute of the General Hospital, Ningxia Medical University, Yinchuan, China * These authors have contributed equally to this work Correspondence to: Wenjun Yang, email: yw001@nxmu.edu.cn Baoguo Liu, email: lbg29@163.com Keywords: papillary thyroid carcinoma (PTC), cancer panel, fusion gene, somatic mutation Received: February 08, 2017     Accepted: April 04, 2017     Published: April 25, 2017 ABSTRACT 138 papillary thyroid carcinoma (PTC) samples were assessed for somatic mutation profile and fusion genes by targeted resequencing using a cancer panel (ThyGenCap TM ) targeting 244 cancer-related genes and 20 potential fusion genes. At least one genetic alteration (including mutations and fusion genes) was observed in 118/138 (85.5%) samples. The most frequently mutated gene was BRAF V600E (57.2%). Moreover, we identified 11 fusion genes including eight previously reported ones and three novel fusion genes, UEVLD-RET , OSBPL9-BRAF , and SQSTM1-NTRK3 . Alterations affecting the mitogen-activated protein kinase (MAPK) signaling pathway components were seen in 69.6% of the PTC cases and all of these driver mutations were mutually exclusive. Univariate analysis ascertained that the fusion genes were strongly associated with distinct clinicopathological characteristics, such as young age, local invasion, extensive metastasis, and disease stage. In conclusion, our approach facilitated simultaneous high-throughput detection of gene fusions and somatic mutations in PTC samples.