Follicular patterned thyroid neoplasms: molecular profile investigation and identification of pre-surgical diagnostic markers

• Grant number: 23/04139-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2024
• End date: February 29, 2028
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Janete Maria Cerutti
• Grantee: Isabela Nogueira Nunes
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Thyroid nodules are commonly identified through palpation of the cervical region or through neck ultrasound. The decision whether it should be subjected to fine needle aspiration (FNAB) is based on the clinical presentation, laboratory tests and ultrasound characteristics of the nodule. The Bethesda System for Reporting Thyroid Cytopathology is the standard system for reporting FNAB results in six diagnostic categories.Among the follicular cell-derived thyroid neoplasms, follicular adenoma (FTA), oncocytic adenoma (OTA), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), follicular carcinoma (FTC), oncocytic carcinoma (OTC), invasive encapsulated follicular variant of papillary thyroid carcinoma (iefPTC) and infiltrative follicular variant (ifPTC), represent one of the biggest problems in diagnostic by FNAB due to the similarity of cytological features and the need to detect histological features that are only observable on surgical biopsy. Thereby, these nodules are commonly grouped into Bethesda III, IV and less frequently, Bethesda V categories.The lack of a specific marker for each one of these histological subtypes lead to overtreatment of nodules that prove to be benign in the histopathological findings and may cause side effects. On the other hand, it can delay the treatment of malignant nodules. Therefore, studies that seek to find a molecular marker that can be applied in pre surgical reality are extremely relevant, since this would make real a better definition of treatment of patients in cases with low risk of malignancy. Therefore, the objective of the project is to identify molecular markers capable of distinguishing NIFTP, iefPTC, ifPTC and FTC, through total RNA sequencing using Illumina NextSeq platform (RNA-seq) and validation of findings in an expanded casuistic.The data will be evaluated using specific pipelines that allow to identify point mutations, gene fusions and differential expression, such as GATK, STAR-fusion and NOISeq (Bioconductior). The pathogenic variants will be validated by PCR followed by Sanger Sequencing. The genic fusions will be validated by RT-qPCR in a expanded casuistic. Among the validated variants, we will select one to analyze the effect on the genesis and progression of thyroid tumors, through a functional study. Furthermore, the identified variants may be included in a panel for molecular diagnosis of thyroid nodules. (AU)