NEXT GENERATION SEQUENCING FOR DETECTION OF MUTATIONS IN THYROID HURTHLE CELL CARCINOMAS

• Grant number: 15/14819-7
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2016
• End date: October 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Debora Lucia Seguro Danilovic
• Grantee: Debora Lucia Seguro Danilovic
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Antonio Marcondes Lerario ; Nathalie Oliveira de Santana ; Suemi Marui

Abstract

The Hürthle cell carcinoma is considered a variant of the follicular thyroid carcinoma, despite distinct clinical behavior. Genetic abnormalities associated to thyroid carcinogenesis have been studied, mainly in papillary and follicular carcinomas. A few gene mutations were identified in Hürthle cell carcinoma, involving mitochondrial genes, RAS e MEN1. However, they were restricted to a small percentage of cases. Nevertheless, gene expression analysis revealed activation of the intracellular signaling pathways, PI3K-AkT-mTOR and Wnt/²-catenina, in extensively invasive Hürthle cell carcinomas. The aims of this study are identify genetic abnormalities associated to Hürthle cell carcinomas using next generation sequencing and analyze their connection with clinical and histological features associated to poor prognosis. Genomic DNA extraction will be performed in paraffin-embedded samples of 48 Hürthle cell carcinomas and respective normal thyroid tissues. One hundred selected genes will be simultaneously sequenced. They are involved in intracellular signaling pathways - Wnt/²-catenina, mTOR, MAPK and Notch-, some are related to follicular cell function and others associated to carcinogenesis. Next generation sequencing will be performed in the sequencing system of large-scale genomics, HiSeq 2500 (Illumina), belonging to the Laboratório de Sequenciamento em Larga Escala (SELA) and acquired with FAPESP grants (2014/50137-5). Finally, the identified abnormalities will be studied in 30 Hürthle cells adenomas in order to elucidate their association with malignant transformation. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTANA, NATHALIE OLIVEIRA; COSTA FREITAS, RICARDO MIGUEL; MARCOS, VINICIUS NEVES; CHAMMAS, MARIA CRISTINA; ASATO CAMARGO, ROSALINDA YOSSIE; SCHMERLING, CLAUDIA KLIEMANN; BRASILEIRO VANDERLEI, FELIPE AUGUSTO; HOFF, ANA OLIVEIRA; MARUIL, SUEMI; SEGURO DANILOVIC, DEBORA LUCIA. Diagnostic performance of thyroid ultrasound in Hürthle cell carcinomas. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 63, n. 3, p. 300-305, MAY-JUN 2019. (15/14819-7)

SANTANA, NATHALIE OLIVEIRA; LERARIO, ANTONIO MARCONDES; SCHMERLING, CLAUDIA KLIEMANN; MARUI, SUEMI; FERREIRA ALVES, VENANCIO AVANCINI; HOFF, ANA O.; KOPP, PETER; SEGURO DANILOVIC, DEBORA LUCIA. Molecular profile of Hurthle cell carcinomas: recurrent mutations in the Wnt/beta-caten n pathway. EUROPEAN JOURNAL OF ENDOCRINOLOGY, v. 183, n. 6, p. 647-656, DEC 2020. (15/14819-7)