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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

Grant number: 14/06570-6
Support type:Research Projects - Thematic Grants
Duration: October 01, 2015 - September 30, 2020
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Janete Maria Cerutti
Grantee:Janete Maria Cerutti
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Co-Principal Investigators:Magnus Régios Dias da Silva ; Rui Monteiro de Barros Maciel
Assoc. researchers: Adriano Namo Cury ; Gianna Maria Griz Carvalheira ; Gilles Landman ; Nilson Ivo Tonin Zanchin ; Pedro Alexandre Favoretto Galante ; Victor Piana de Andrade
Associated scholarship(s):18/13203-0 - New insights into the prognosis of papillary thyroid microcarcinoma: mutational status analysis of BRAF V600E and whole exome sequencing, BP.DD
18/09911-0 - AGK-BRAF in pediatric papillary thyroid carcinoma: investigation of the mechanism associated with the high rate and functional analysis, BP.DR
17/12107-5 - Investigation of molecular markers for the diagnosis of MEN 2 through metabolic profile of HEK293 cells with RET expression and MEN 2/RET patients, BP.DR
+ associated scholarships 17/14948-7 - Study of LIMD2 role on thyroid cancer epithelial-mesenchymal transition, BP.PD
15/13413-7 - Investigation of chromosomal rearrangements in the BRAF gene in differentiated thyroid carcinomas in childhood, BP.MS
12/17545-7 - Molecular characterization of thyroid tumors using whole exome sequencing: search for diagnostic molecular markers, BP.PD - associated scholarships

Abstract

The prevalence of thyroid nodules depends on several factors such as age, population studied, sex and method of evaluation. Due to the use of high-resolution ultrasound, which can detect nodules as small as 2 mm, the prevalence of thyroid nodules has increased, reaching up to 67 %. As a consequence of the increase in the diagnosis of the nodules, we also observed an increased incidence of thyroid cancer. Currently, thyroid cancer is the fastest growing cancer incidence worldwide. According to the National Cancer Institute (INCA), thyroid neoplasms represent 5.6% of cancers in women, currently being the fourth most common type of cancer in the female Brazilian adult population. It is suggested that this trend is directly related to the increased frequency of papillary thyroid carcinoma and its variants. In fact, approximately 50 % of the increase was at the expense of the diagnosis of micropapillary carcinomas (tumors d 1 cm). Similar to adults, the incidence rate of pediatric thyroid cancer has also increased, being the papillary histological type the most prevalent subtype. This project will address clinical problems related to diagnosis and prognosis of thyroid nodules. Primarily, we sought to identify new genetic events associated with the genesis of different thyroid carcinoma subtypes that can be used as preoperative diagnostic markers that can help the distinction of nodules commonly classified as indeterminate that occur both in the adult or pediatric ages. We believe that the identification of these new markers will enable us to develop a diagnostic test, which may have increased sensitivity and specificity of the tests currently available. Also aims to identify markers capable of predicting the prognosis of thyroid nodules, particularly micropapillary carcinomas. It also seeks to contribute to the determination of genetic events associated with the genesis and progression of medullary thyroid carcinoma occurring in sporadic and hereditary forms. As a strategy to identify new recurrent somatic mutations and/or gene fusion events, we will use whole exome sequencing and/or RNA (paired-end RNA sequencing) or Target Ressenquencing, since 85% of the disease-causing mutations are located in coding regions of the genome. These strategies have achieved high levels of success in identifying genes associated with diseases, especially in cancer. In addition to identifying new genetic events, this project also aims to characterize the signaling pathway associated with new genes and new mutations previously identified in thyroid cancer by our group. This is an innovative proposal whose results may have immediate clinical application, as well as may contribute in the identification of new signaling pathways involved in the genesis and progression of tumors of the thyroid and thus open new perspectives for targeted therapy. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Biomarkers confirm a higher incidence of thyroid cancer among World Trade Center responders 
Articles published in other media outlets (27 total):
More itemsLess items
Socorristas das torres gêmeas têm maior incidência de câncer de tireoide 
Socorristas das torres gêmeas têm maior incidência de câncer de tireoide 
Biomarcadores confirmam maior incidência de câncer de tireoide em socorristas das torres gêmeas 
11 de Setembro: maior incidência de câncer de tireoide entre socorristas 
Biomarkers Confirm a Higher Incidence of Thyroid Cancer Among World Trade Center Responders 
Confirman mayor incidencia de cáncer tiroideo en rescatadores de las torres gemelas 
Biomarcadores confirman una mayor incidencia de cáncer tiroideo en rescatadores de las torres gemelas 
Biomarcadores confirman una mayor incidencia de cáncer tiroideo en rescatadores de las torres gemelas 
Biomarkers reveal increase in thyroid cancer incidence among WTC responders 
Biomarkers reveal increase in thyroid cancer incidence among WTC responders 
Biomarkers confirm higher incidence of thyroid cancer among World Trade Center responders 
Biomarkers Confirm Higher Incidence Of Thyroid Cancer Among World Trade Center Responders 
Thyroid Cancer Three Times Higher Among World Trade Center Responders 
Biomarkers confirm higher incidence of thyroid cancer among World Trade Center responders 
Biomarkers confirm higher incidence of thyroid cancer among World Trade Center responders 
Biomarkers confirm higher incidence of thyroid cancer among World Trade Center responders 
Biomarkers confirm higher incidence of thyroid cancer among respondents from the World Trade Center 
Biomarkers confirm higher incidence of thyroid cancer among World Trade Center responders 
Biomarcadores confirmam maior incidência de câncer de tireoide em socorristas das torres gêmeas 
11 de Setembro: maior incidência de câncer de tireoide entre socorristas 
Biomarcadores confirmam maior incidência de câncer de tireoide em socorristas das torres gêmeas 
Biomarcadores confirmam maior incidência de câncer de tireoide em socorristas das torres gêmeas 
Biomarcadores confirmam maior incidência de câncer de tireoide em socorristas das torres gêmeas 
Há maior incidência de câncer de tireoide em socorristas das torres gêmeas 
Biomarcadores confirmam maior incidência de câncer de tireoide em socorristas das torres gêmeas – 19/07/2019 – Eq 
11 de Setembro: maior incidência de câncer entre socorristas 
Socorristas das torres gêmeas tem maior incidência de câncer de tireoide - Jornal Notícias 

Scientific publications (15)
(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)
RADONSKY, VANESSA; KIZYS, MARINA MALTA LETRO; DOTTO, RENATA PIRES; ESPER, PRISCILA LIGEIRO GONCALVES; HEILBERG, ITA PFEFERMAN; DIAS-DA-SILVA, MAGNUS REGIOS; LAZARETTI-CASTRO, MARISE. Hypomagnesemia with Hypercalciuria Leading to Nephrocalcinosis, Amelogenesis Imperfecta, and Short Stature in a Child Carrying a Homozygous Deletion in theCLDN16Gene. CALCIFIED TISSUE INTERNATIONAL, JUL 2020. Web of Science Citations: 0.
ARALDI, RODRIGO PINHEIRO; KHALIL, CHARBEL; GRIGNET, PEDRO HENRIQUE; TEIXEIRA, MICHELLI RAMIRES; DE MELO, THATIANA CORREA; MODOLO, DIEGO GRANDO; VIRGILIO FERNANDES, LUIS GUILHERME; RUIZ, JORGE; DE SOUZA, EDISLANE BARREIROS. Medical applications of clustered regularly interspaced short palindromic repeats (CRISPR/Cas) tool: A comprehensive overview. Gene, v. 745, JUN 30 2020. Web of Science Citations: 0.
WILLIAMSON, TARA; MENDES, THAIS BIUDE; JOE, NATALIE; CERUTTI, JANETE M.; RIGGINS, GREGORY J. Mebendazole inhibits tumor growth and prevents lung metastasis in models of advanced thyroid cancer. Endocrine-Related Cancer, v. 27, n. 3, p. 123-136, MAR 2020. Web of Science Citations: 0.
VARGAS, MICHELLE CERUTTI C.; MOURA, FELIPE SCIPIAO; ELIAS, CECILIA P.; CARVALHO, SARA R.; RASSI, NELSON; KUNII, ILDA S.; DIAS-DA-SILVA, MAGNUS R.; COSTA-BARBOSA, FLAVIA AMANDA. Spontaneous fertility and variable spectrum of reproductive phenotype in a family with adult-onset X-linked adrenal insufficiency harboring a novel DAX-1/NR0B1 mutation. BMC Endocrine Disorders, v. 20, n. 1 FEB 6 2020. Web of Science Citations: 0.
CARVALHEIRA, GIANNA; MALINVERNI, ANDREA M.; MOYSES-OLIVEIRA, MARIANA; UETA, RENATA; CARDILI, LEONARDO; MONTEAGUDO, PATRICIA; MATHEZ, ANDREIA L. G.; VERRESCHI, IEDA T.; MALUF, MIGUEL A.; SHIDA, MARCIA E. F.; LEITE, MILA T. C.; MAZZOTTI, DIEGO; MELARAGNO, MARIA ISABEL; DIAS-DA-SILVA, MAGNUS R. The Natural History of a Man With Ovotesticular 46,XX DSD Caused by a Novel 3-Mb 15q26.2 Deletion Containing NR2F2 Gene. JOURNAL OF THE ENDOCRINE SOCIETY, v. 3, n. 11, p. 2107-2113, NOV 2019. Web of Science Citations: 0.
DE JESUS PANIZA, ANA CAROLINA; MENDES, THAIS BIUDE; BORGES VIANNA, MATHEUS DUARTE; DIAS THOMAZ, DEBORA MOTA; CHIAPPINI, PAULA B. O.; COLAZZA-GAMA, GABRIEL A.; LINDSEY, SUSAN CHOW; DE CARVALHO, MARCOS BRASILINO; FERREIRA ALVES, VENANCIO AVANCINI; CURIONI, OTAVIO; BASTOS, ANDRE UCHIMURA; CERUTTI, JANETE MARIA. Revised criteria for diagnosis of NIFTP reveals a better correlation with tumor biological behavior. ENDOCRINE CONNECTIONS, v. 8, n. 11, p. 1529-1538, NOV 2019. Web of Science Citations: 0.
BIM, LARISSA V.; NAVARRO, FABIO C. P.; VALENTE, FLAVIA O. F.; LIMA-JUNIOR, JOSE V.; DELCELO, ROSANA; DIAS-DA-SILVA, MAGNUS R.; MACIEL, RUI M. B.; GALANTE, PEDRO A. F.; CERUTTI, JANETE M. Retroposed copies of RET gene: a somatically acquired event in medullary thyroid carcinoma. BMC MEDICAL GENOMICS, v. 12, JUL 9 2019. Web of Science Citations: 0.
SISDELLI, LUIZA; CUNHA VIEIRA CORDIOLI, MARIA ISABEL; VAISMAN, FERNANDA; MORAES, LAIS; COLOZZA-GAMA, GABRIEL AVELAR; ALVES, JR., PAULO ALONSO G.; ARAUJO, JR., MARIO LUCIO; SEIXAS ALVES, MARIA TERESA; MONTE, OSMAR; LONGUI, CARLOS ALBERTO; CURY, ADRIANO NAMO; CARVALHEIRA, GIANNA; CERUTTI, JANETE MARIA. AGK-BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma. PEDIATRIC BLOOD & CANCER, v. 66, n. 7 JUL 2019. Web of Science Citations: 2.
MACIEL, RUI M. B.; CAMACHO, CLEBER P.; ASSUMPCAO, LIGIA V. M.; BUFALO, NATASSIA E.; CARVALHO, ANDRE L.; DE CARVALHO, GISAH A.; CASTRONEVES, LUCIANA A.; DE CASTRO JR, FRANCISCO M.; CEOLIN, LUCIELI; CERUTTI, JANETE M.; CORBO, ROSSANA; FERRAZ, TANIA M. B. L.; FERREIRA, V, CARLA; FRANCA, M. INEZ C.; GALVAO, HENRIQUE C. R.; GERMANO-NETO, FAUSTO; GRAF, HANS; JORGES, ALEXANDER A. L.; KUNII, ILDA S.; LAURIA, MARCIO W.; LEAL, VERA L. G.; LINDSEY, SUSAN C.; LOURENCO JR, DELMAR M.; MADER, LEA M. Z.; MAGALHAES, PATRICIA K. R.; MARTINS, JOAO R. M.; CECILIA MARTINS-COSTA, M.; MAZETOR, GLAUCIA M. F. S.; IMPELLIZZERI, ANELISE I.; NOGUEIRA, CELIA R.; PALMERO, I, EDENIR; PESSOA, CENCITA H. C. N.; PRADA, BIBIANA; SIQUEIRA, DEBORA R.; SOUSA, MARIA SHARMILA A.; TOLEDO, RODRIGO A.; VALENTE, FLAVIA O. F.; VAISMAN, FERNANDA; WARD, LAURA S.; WEBER, SHANA S.; WEISS, V, RITA; YANG, JI H.; DIAS-DA-SILVA, MAGNUS R.; HOFF, ANA O.; TOLEDO, SERGIO P. A.; MAIA, ANA L. Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study. ENDOCRINE CONNECTIONS, v. 8, n. 3, p. 289-298, MAR 2019. Web of Science Citations: 3.
NOZIMA, BRUNO HEIDI; MENDES, THAIS BIUDE; DA SILVA PEREIRA, GUSTAVO JOSE; ARALDI, RODRIGO PINHEIRO; MIAZATO IWAMURA, EDNA SADAYO; SMAILI, SORAYA SOUBHI; GRIZ CARVALHEIRA, GIANNA MARIA; CERUTTI, JANETE MARIA. FAM129A regulates autophagy in thyroid carcinomas in an oncogene-dependent manner. Endocrine-Related Cancer, v. 26, n. 1, p. 227-238, JAN 2019. Web of Science Citations: 2.
CARREGOSA PINHEIRO DOS SANTOS, MARIA JOSE; BASTOS, ANDRE UCHIMURA; DA COSTA, VITOR RODRIGUES; DELCELO, ROSANA; LINDSEY, SUSAN CHOW; COLOZZA-GAMA, GABRIEL AVELAR; PENG, HONGZHUANG; RAUSCHER, III, FRANK J.; OLER, GISELE; CERUTTI, JANETE MARIA. LIMD2 Is Overexpressed in BRAF V600E-Positive Papillary Thyroid Carcinomas and Matched Lymph Node Metastases. ENDOCRINE PATHOLOGY, v. 29, n. 3, p. 222-230, SEP 2018. Web of Science Citations: 3.
CUNHA, LUCAS L.; LINDSEY, SUSAN C.; FRANCA, MARIA INEZ C.; SARIKA, LEDA; PAPATHOMA, ALEXANDRA; KUNII, ILDA S.; CERUTTI, JANETE M.; DIAS-DA-SILVA, MAGNUS R.; ALEVIZAKI, MARIA; MACIEL, RUI M. B. Evidence for the founder effect of RET533 as the common Greek and Brazilian ancestor spreading multiple endocrine neoplasia 2A. EUROPEAN JOURNAL OF ENDOCRINOLOGY, v. 176, n. 5, p. 515-519, MAY 2017. Web of Science Citations: 7.
MARTINS-COSTA, M. CECLIA; CUNHA, LUCAS L.; LINDSEY, SUSAN C.; CAMACHO, CLEBER P.; DOTTO, RENATA P.; FURUZAWA, GILBERTO K.; SOUSA, M. SHARMILA A.; KASAMATSU, TERESA S.; KUNII, ILDA S.; MARTINS, MRCIO M.; MACHADO, ALBERTO L.; MARTINS, JOAO R. M.; DIAS-DA-SILVA, MAGNUS R.; MACIEL, RUI M. B. M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds. Endocrine-Related Cancer, v. 23, n. 12, p. 909-920, DEC 2016. Web of Science Citations: 8.
MENDES, THAIS BIUDE; NOZIMA, BRUNO HEIDI; BUDU, ALEXANDRE; DE SOUZA, RODRIGO BARBOSA; BRAGA CATROXO, MARCIA HELENA; DELCELO, ROSANA; GAZARINI, MARCOS LEONI; CERUTTI, JANETE MARIA. PVALB diminishes [Ca2+] and alters mitochondrial features in follicular thyroid carcinoma cells through AKT/GSK3 beta pathway. Endocrine-Related Cancer, v. 23, n. 9, p. 769-782, SEP 2016. Web of Science Citations: 1.
CORDIOLI, MARIA ISABEL C. V.; MORAES, LAIS; CARVALHEIRA, GIANNA; SISDELLI, LUIZA; ALVES, MARIA TERESA S.; DELCELO, ROSANA; MONTE, OSMAR; LONGUI, CARLOS A.; CURY, ADRIANO N.; CERUTTI, JANETE M. AGK-BRAF gene fusion is a recurrent event in sporadic pediatric thyroid carcinoma. CANCER MEDICINE, v. 5, n. 7, p. 1535-1541, JUL 2016. Web of Science Citations: 10.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.