Journal
CANCERS
Volume 12, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/cancers12061597
Keywords
TERT; papillary thyroid carcinoma; gene expression profile
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Funding
- National Centre for Research and Development project under the program Prevention practices and treatment of civilization diseases STRATEGMED [STRATEGMED2/267398/4/NCBR/2015]
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Background: Telomerase reverse transcriptase promoter (TERTp) mutations are related to a worse prognosis in various malignancies, including papillary thyroid carcinoma (PTC). Since mechanisms responsible for the poorer outcome of TERTp(+) patients are still unknown, searching for molecular consequences ofTERTp mutations in PTC was the aim of our study. Methods: The studied cohort consisted of 54 PTCs, among them 24 cases with distant metastases.BRAFV600E,RAS,andTERTp mutational status was evaluated in all cases. Differences in gene expression profile between TERTp(+) and TERTp(-) PTCs were examined using microarrays. The evaluation of signaling pathways and gene ontology was based on the Gene Set Enrichment Analysis. Results: Fifty-nine percent (32/54) of analyzed PTCs were positive for at least one mutation: 27 were BRAF(+), among them eight were TERTp(+), and 1 NRAS(+), whereas five other samples harboredRASmutations. Expression of four genes significantly differed in BRAF(+)TERTp(+) and BRAF(+)TERTp(-) PTCs. Deregulation of pathways involved in key cell processes was observed. Conclusions:TERTp mutations are related to higher PTC aggressiveness.CRABP2gene was validated as associated withTERTp mutations. However, its potential use in diagnostics or risk stratification in PTC patients needs further studies.
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