한빛사 논문
Seong-Keun Yoo1,2,3,14, Young Shin Song4,5,14, Eun Kyung Lee6, Jinha Hwang7, Hwan Hee Kim4, Gyeongseo Jung4, Young A Kim8, Su-jin Kim9, Sun Wook Cho4, Jae-Kyung Won10, Eun-Jae Chung11, Jong-Yeon Shin1,3, Kyu Eun Lee1,9, Jong-Il Kim1,7, Young Joo Park1,4,15,* & Jeong-Sun Seo1,3,7,12,13,15,*
1 Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 03080, Republic of Korea. 2 Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 08826, Republic of Korea. 3 Macrogen Inc., Seoul 08511, Republic of Korea. 4 Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. 5 Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam 13496, Republic of Korea. 6 Center for Thyroid Cancer, National Cancer Center, Goyang 10408, Republic of Korea. 7 Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Republic of Korea. 8 Department of Pathology, Seoul National University Boramae Medical Center, Seoul 07061, Republic of Korea. 9 Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. 10 Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. 11 Department of Otorhinolaryngology- Head and Neck Surgery, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. 12 Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam, Bundang-gu, Gyeonggi-do 13605, Republic of Korea. 13 Gong-Wu Genomic Medicine Institute, Seoul National University Bundang Hospital, Seongnam 13605, Republic of Korea. 14 These authors contributed equally: Seong-Keun Yoo, Young Shin Song. 15 These authors jointly supervised this work: Young Joo Park, Jeong-Sun Seo.
*Correspondence and requests for materials should be addressed to Y.J.P. or to J.-S.S.
Abstract
Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT, AKT1, PIK3CA, and EIF1AX were frequently co-mutated with driver genes (BRAFV600E and RAS) in advanced DTCs as well as ATC, but tumor suppressors (e.g., TP53 and CDKN2A) were predominantly altered in ATC. CDKN2A loss was significantly associated with poor disease-specific survival in patients with ATC or advanced DTCs, and up-regulation of CD274 (PD-L1) and PDCD1LG2 (PD-L2). Transcriptome analysis revealed a fourth molecular subtype of thyroid cancer (TC), ATC-like, which hardly reflects the molecular signatures in DTC. Furthermore, the activation of JAK-STAT signaling pathway could be a potential druggable target in RAS-positive ATC. Our findings provide insights for precision medicine in patients with advanced TCs.
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