Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer

Autor: Hwan Hee Kim, Young Shin Song, Jong Il Kim, Gyeongseo Jung, Jae Kyung Won, Seong Keun Yoo, Jinha Hwang, Young A. Kim, Su Jin Kim, Sun Wook Cho, Eun Jae Chung, Kyu Eun Lee, Eun Kyung Lee, Jeong-Sun Seo, Jong Yeon Shin, Young Joo Park
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
endocrine system diseases
Thyroid Gland
General Physics and Astronomy
02 engineering and technology
Thyroid Carcinoma
Anaplastic
Transcriptome
CDKN2A
Cancer genomics
Precision Medicine
lcsh:Science
Thyroid cancer
Multidisciplinary
Thyroid
High-Throughput Nucleotide Sequencing
Genomics
Middle Aged
021001 nanoscience & nanotechnology
Up-Regulation
Gene Expression Regulation
Neoplastic
STAT Transcription Factors
medicine.anatomical_structure
Disease Progression
Female
0210 nano-technology
Signal Transduction
Adult
endocrine system
Science
EIF1AX
General Biochemistry
Genetics and Molecular Biology
Article
Thyroid carcinoma
03 medical and health sciences
Cell Line
Tumor
medicine
Biomarkers
Tumor
Humans
Thyroid Neoplasms
Anaplastic thyroid cancer
Aged
Janus Kinases
business.industry
Gene Expression Profiling
General Chemistry
medicine.disease
Survival Analysis
Gene expression profiling
030104 developmental biology
Mutation
Cancer research
lcsh:Q
business
Zdroj: Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019)
Nature Communications
ISSN: 2041-1723
Popis: 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.
Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) come with a dismal prognosis. Here, Yoo and colleagues reveal the genomic and transcriptomic landscape of ATC and DTC, highlighting potential therapeutic vulnerabilities.
Databáze: OpenAIRE
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