New insights into the prognosis of papillary thyroid microcarcinoma: mutational status analysis of BRAF V600E and whole exome sequencing

• Grant number: 18/13203-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2019
• End date: May 31, 2022
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Janete Maria Cerutti
• Grantee: Gabriel Avelar Colozza Gama
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 14/06570-6 - Comprehensive whole exome, paired-end RNA and genome sequencing: new insights into genetic bases of thyroid carcinoma in pediatric and adult ages and applications in clinical practice, AP.TEM

Abstract

Papillary Thyroid Carcinoma (PTC) is the most common subtype of Thyroid Cancer and is also the one with the highest incidence increase in recent years. The increase in the prevalence is mainly due to the increase in the diagnostic rates of small tumors, with at least 50% being tumors with a size of 1cm or less, called microcarcinomas (microPTC). In general, these tumors are considered highly indolent, with low recurrence rate and high survival rate. However, approximately 30% of the cases may have more aggressive behavior. Even so, the vast majority of microcarcinomas follow the recommended treatment for tumors> 1cm. In addition to the likelihood of complications due to microcarcinoma thyroidectomy, such as hypocalcemia, there are costs associated with the procedure that can burden the public system, such as the need for hormone replacement and others. The identification of pre-surgical diagnostic and prognostic markers can aid in the management, diagnosis and clinical or surgical treatment. In this way, it allows better selection of patients referred for surgery, besides allowing determination of the type and extent of surgery. Although there are few studies on the use of prognostic markers in microPTC cases, the BRAF V600E mutation has been associated with a worse prognosis in PTC cases of > 1cm in size. It has been suggested that in addition to identifying the BRAF V600E mutation, determining the percentage of cells with the presence of the mutation can provide information related to the biological behavior of the tumor. Thus, we propose to investigate the presence of the BRAF V600E mutation and to evaluate the percentage of cells with presence of the V600E allele in the primary tumor (d 10mm) and paired metastases, by means of the pyosequencing technique to determine if, in addition to the mutation, determining the percentage of mutated cells may play a relevant role in the prognosis of microPTCs. For this, the mutational status of the samples will be correlated with the demographic and clinical-pathological data. Subsequently, in order to identify new prognostic and predictive markers, we will select the cases that present a more aggressive and negative biological behavior for BRAF V600E, besides selecting positive cases for the mutation in order to search for genes that can collaborate with BRAF. The selected cases will be submitted to sequencing and analysis of the complete exome. This is an original study that should aid in the diagnosis and prognosis of the thyroid nodules. (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)

COLOZZA-GAMA, GABRIEL A.; CALLEGARI, FABIANO; BESIC, NIKOLA; PAVIZA, ANA C. DE J.; CERUTTI, JANETE M.. Machine learning algorithm improved automated droplet classification of ddPCR for detection of BRAF V600E in paraffin-embedded samples. SCIENTIFIC REPORTS, v. 11, n. 1, JUN 16 2021. (18/13203-0, 14/06570-6, 18/23497-1)

ARALDI, RODRIGO PINHEIRO; DE MELO, THATIANA CORREA; LEVY, DEBORA; DE SOUZA, DENER MADEIRO; MAURICIO, BEATRIZ; COLOZZA-GAMA, GABRIEL AVELAR; BYDLOWSKI, SERGIO PAULO; PENG, HONGZHUANG; RAUSCHER, III, FRANK J.; CERUTTI, JANETE MARIA. LIMD2 Regulates Key Steps of Metastasis Cascade in Papillary Thyroid Cancer Cells via MAPK Crosstalk. CELLS, v. 9, n. 11, NOV 2020. (17/14948-7, 14/06570-6, 18/13203-0)

DA COSTA, VITOR RODRIGUES; BIM, LARISSA VALDEMARIN; SILVA, LUIZA DORNELLES PENTEADO E; COLLOZA-GAMA, GABRIEL AVELAR; BASTOS, ANDRE UCHIMURA; DELCELO, ROSANA; OLER, GISELE; CERUTTI, JANETE MARIA. Advances in Detecting Low Prevalence Somatic TERT Promoter Mutations in Papillary Thyroid Carcinoma. FRONTIERS IN ENDOCRINOLOGY, v. 12, MAR 12 2021. (14/06570-6, 12/06221-6, 12/17545-7, 18/13203-0)