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Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer
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Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer
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Journal Article
Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer
2019
Overview
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
V600E
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/77
/ 38/91
/ 45/88
/ 49/105
/ 49/23
/ Adult
/ Aged
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Cancer
/ DNA
/ Female
/ Gene Expression Regulation, Neoplastic - genetics
/ Genomics
/ High-Throughput Nucleotide Sequencing
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mutation
/ Precision Medicine - methods
/ RNA
/ Science
/ Signal Transduction - genetics
/ STAT Transcription Factors - metabolism
/ Thyroid
/ Thyroid Carcinoma, Anaplastic - genetics
/ Thyroid Carcinoma, Anaplastic - mortality
/ Thyroid Carcinoma, Anaplastic - pathology
/ Thyroid Carcinoma, Anaplastic - therapy
/ Thyroid Neoplasms - genetics
/ Thyroid Neoplasms - mortality
