Pediatric Papillary Thyroid Carcinoma: Identification of Prognostic Markers Capable of Predicting the Risk of Persistent or Recurrent Disease via RNA Sequencing

• Grant number: 24/08427-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2024
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Janete Maria Cerutti
• Grantee: Júlia Helena Tezzei
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

An increase in the incidence rates of thyroid carcinoma has been observed around the world, both in the adult and pediatric population. Papillary Thyroid Carcinoma (PTC) is the most prevalent subtype, comprising approximately 80% of cases. The clinical presentation of adult and pediatric PTC cases is distinct. In pediatric cases, thyroid cancer generally presents in a single nodule, which has a higher risk of malignancy than adults, and is more likely to be presented at a more advanced stage at diagnosis. Among the genetic changes identified in CPT, there is a high prevalence of changes in genes that encode proteins associated with RAS/RAF/MER/ERK signaling, also called the MAPK (Mitogen-activated protein kinase) pathway. Point mutations in BRAF V600E genes and RAS family genes are the most common genetic events in adult PTC, and gene fusions (RET/PTC, AGK::BRAF, ETV6::NTRK3 and STRN::ALK) are the most common frequently observed in pediatric CPT. Therapy with 131I (RAI, radioactive iodine) is the adjuvant treatment to thyroidectomy commonly used in clinical practice. Refractoriness to 131I treatment, caused by decreased expression or decreased targeting of the NIS protein to the cell membrane, has been associated with the constitutive activation of the MAPK pathway and underlying the dedifferentiation process. Studies from Our Group demonstrate that low NIS expression in patients is related to a higher recurrence rate, specifically in cases of pediatric PTC. Therefore, the present work aims to investigate the mutational profile, in addition to the gene expression profile, associated with disease progression and low treatment response rates, evidenced by the presence of biochemical and/or structural disease. We believe that the results from this project will help to elucidate the understanding of the molecular profile mechanism in the pathogenesis and progression of pediatric PTC.