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


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.

SUBMITTER: Yoo SK 

PROVIDER: S-EPMC6591357 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Yoo Seong-Keun SK   Song Young Shin YS   Lee Eun Kyung EK   Hwang Jinha J   Kim Hwan Hee HH   Jung Gyeongseo G   Kim Young A YA   Kim Su-Jin SJ   Cho Sun Wook SW   Won Jae-Kyung JK   Chung Eun-Jae EJ   Shin Jong-Yeon JY   Lee Kyu Eun KE   Kim Jong-Il JI   Park Young Joo YJ   Seo Jeong-Sun JS  

Nature communications 20190624 1


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 (BRAF<sup>V600E</sup> and RAS) in advanced DTCs as well as ATC, but tumor suppressors (e.g., TP53 and CDKN2A) we  ...[more]

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