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Master's Dissertation
DOI
https://doi.org/10.11606/D.87.2014.tde-08052014-163253
Document
Author
Full name
Ana Carolina Bernardini Moulatlet
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Severino, Patrícia (President)
Leite, Katia Ramos Moreira
Maria, Durvanei Augusto
Title in Portuguese
MicroRNAs como biomarcadores no carcinoma papilífero de tireóide: associação com mutações somáticas frequentes e significado biológico.
Keywords in Portuguese
Biomarcadores
Carcinoma papilar
Expressão gênica
Glândula tireóide
Mutações genéticas
Abstract in Portuguese
Os microRNAs são pequenos RNAs importantes na modulação da expressão gênica. O carcinoma papilífero de tireoide (CPT) é responsável pela maior parte dos casos de câncer de tireoide. Mutações somáticas ativam as vias de MAPK e PI3K/AKT e exercem papel importante no desenvolvimento do CPT. Acredita-se que miRNAs regulem genes associados a essas vias. A expressão de miRNAs foi avaliada em amostras parafinadas de CPT caracterizadas quanto à presença da mutação BRAFV600E. A expressão de miRNAs variou devido à heterogeneidade dos tecidos emblocados e entre pacientes, dados importantes quando microRNAs são avaliados como biomarcadores. Microarranjos de DNA mostraram diferenças na expressão de miR-16, miR-19a, miR-21, miR146a, miR-146b, miR-221 e miR-222 entre amostras positivas e negativas para BRAFV600E, indicando um possível papel na modulação de vias influenciadas por esta mutação. Quando amostras adicionais foram analisadas, apenas miR-146b apresentou expressão diferencial entre os dois grupos, ressaltando a variabilidade entre pacientes quanto à expressão de miRNAs.
Title in English
MicroRNAs as biomarkers in papillary thyroid cancer: association with frequent somatic mutations and biological significance.
Keywords in English
Biomarkers
Gene expression
Genetic mutations
Papillary carcinoma
Thyroid gland
Abstract in English
MicroRNAs are small non-coding RNAs that regulate protein-coding genes. Papillary thyroid cancer (PTC) accounts for most of the thyroid cancer cases. Somatic mutations activate MAPK and PI3K/AKT pathways and play a leading role in PTC. MiRNAs may contribute to the regulation of these pathways. We studied the expression of miRNAs in formalin-fixed, paraffin-embedded (FFPE) PTC samples submitted to mutation characterization. Our results show that miRNA expression varies due to embedded sample heterogeneity and that there is great variability in miRNA expression among patients, both important issues when miRNA expression is evaluated as a biomarker. DNA microarray experiments compared BRAFV600E positive and negative samples. MiR-16, miR-19a miR-21, miR146a, MiR-146b, miR-221 and miR-222 were deregulated, indicating a possible implication in BRAF-related pathways. When additional samples were evaluated, only miR-146b presented consistent variation in expression, highlighting variability among patients
 
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Publishing Date
2014-05-20
 
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