CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Transcriptomic-based master regulators screening in papillary thyroid carcinoma
Autor/es:
SALUSTRI, G; MARTI, MA; MIRANDA, L; SCHUSTER, DC; NICOLA, JP; GEYSELS, RC; SOSA, EJ
Lugar:
Buenos Aires
Reunión:
Congreso; XVII Latin American Thyroid Society Congress; 2019
Institución organizadora:
Latin American Thyroid Society
Resumen:
Gene expression profile in acellular context is the reflection of specific regulatory programs. A smallnumber of master regulator-acting transcription factors coordinate tumorphenotype. Interestingly, master regulators are increasingly emerging asoptimal biomarkers and therapeutic targets.To uncover master regulators,whose aberrant activity is both necessary and sufficient to maintain thebiological phenotype of papillary thyroid carcinoma.RNA-seq data was obtained fromThe Cancer Genome Atlas. Differential gene expression was computed usingDEseq2. Transcription factor-centered networks were inferred using ARACNe-APalgorithm. Master Regulators were inferred using VIPER analysis.We generated a papillary thyroidcarcinoma-specific transcription factor-centered gene regulatory network. Masterregulator analysis considering differential gene expression in tumor andpaired-normal samples revealed several master regulator-putative transcriptionfactors in BRAF and RAS-like papillary thyroid tumors. Master regulatorsdriving BRAF and RAS-like tumor phenotypes do not overlap. Significantly, weidentified several master regulators?GATAD2A, ETV5, and PROX1?previouslyinvolved in thyroid carcinogenesis. Moreover, we evidenced master regulatorsconnected to a regulon controlling NF-κB signal pathway.Using high-throughputtranscriptomic data, we uncovered a set of master regulator-actingtranscription factors that differentially coordinate BRAF and RAS-likepapillary thyroid tumor phenotype. A comprehensive understanding of masterregulators-promoting thyroid cancer will provide novel diagnostic andtherapeutic applications.