Dataset Information

Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers.

ABSTRACT:

Background

Comprehensive molecular studies on tumours are needed to delineate immortalization process steps and identify sensitive prognostic biomarkers in thyroid cancer.

Methods and results

In this study, we extensively characterize telomere-related alterations in a series of 106 thyroid tumours with heterogeneous clinical outcomes. Using a custom-designed RNA-seq panel, we identified five telomerase holoenzyme-complex genes upregulated in clinically aggressive tumours compared to tumours from long-term disease-free patients, being TERT and TERC denoted as independent prognostic markers by multivariate regression model analysis. Characterization of alterations related to TERT re-expression revealed that promoter mutations, methylation and/or copy gains exclusively co-occurred in clinically aggressive tumours. Quantitative-FISH (fluorescence in situ hybridization) analysis of telomere lengths showed a significant shortening in these carcinomas, which matched with a high proliferative rate measured by Ki-67 immunohistochemistry. RNA-seq data analysis indicated that short-telomere tumours exhibit an increased transcriptional activity in the 5-Mb-subtelomeric regions, site of several telomerase-complex genes. Gene upregulation enrichment was significant for specific chromosome-ends such as the 5p, where TERT is located. Co-FISH analysis of 5p-end and TERT loci showed a more relaxed chromatin configuration in short telomere-length tumours compared to normal telomere-length tumours.

Conclusions

Overall, our findings support that telomere shortening leads to a 5p subtelomeric region reorganization, facilitating the transcription and accumulation of alterations at TERT-locus.

SUBMITTER: Montero-Conde C

PROVIDER: S-EPMC9386325 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers.

Montero-Conde Cristina C Leandro-García Luis Javier LJ Martínez-Montes Ángel M ÁM Martínez Paula P Moya Francisco J FJ Letón Rocío R Gil Eduardo E Martínez-Puente Natalia N Guadalix Sonsoles S Currás-Freixes Maria M García-Tobar Laura L Zafon Carles C Jordà Mireia M Riesco-Eizaguirre Garcilaso G González-García Patricia P Monteagudo María M Torres-Pérez Rafael R Mancikova Veronika V Ruiz-Llorente Sergio S Pérez-Martínez Manuel M Pita Guillermo G Galofré Juan Carlos JC Gonzalez-Neira Anna A Cascón Alberto A Rodríguez-Antona Cristina C Megías Diego D Blasco María A MA Caleiras Eduardo E Rodríguez-Perales Sandra S Robledo Mercedes M

Clinical and translational medicine 20220801 8

<h4>Background</h4>Comprehensive molecular studies on tumours are needed to delineate immortalization process steps and identify sensitive prognostic biomarkers in thyroid cancer.<h4>Methods and results</h4>In this study, we extensively characterize telomere-related alterations in a series of 106 thyroid tumours with heterogeneous clinical outcomes. Using a custom-designed RNA-seq panel, we identified five telomerase holoenzyme-complex genes upregulated in clinically aggressive tumours compared ...[more]

PMID: 35979662

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Dataset Information

Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers.

Background

Methods and results

Conclusions

Publications

Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers.

Similar Datasets

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