title: Comprehensive assessment of the disputed RET Y791F variant shows no association with medullary thyroid carcinoma susceptibility.
abstract: Accurate interpretation of germline mutations of the rearranged during transfection (RET) proto-oncogene is vital for the proper recommendation of preventive thyroidectomy in medullary thyroid carcinoma (MTC)-prone carriers. To gain information regarding the most disputed variant of RET, ATA-A Y791F, we sequenced blood DNA samples from a cohort of 2904 cancer-free elderly individuals (1261 via Sanger sequencing and 1643 via whole-exome/genome sequencing). We also accessed the exome sequences of an additional 8069 individuals from non-cancer-related laboratories and public databanks as well as genetic results from the Catalogue of Somatic Mutations in Cancer (COSMIC) project. The mean allelic frequency observed in the controls was 0.0031, with higher occurrences in Central European populations (0.006/0.008). The prevalence of RET Y791F in the control databases was extremely high compared with the 40 known RET pathogenic mutations (P=0.00003), while no somatic occurrence has been reported in tumours. In this study, we report new, unrelated Brazilian individuals with germline RET Y791F-only: two tumour-free elderly controls; two individuals with sporadic MTC whose Y791F-carrying relatives did not show any evidence of tumours; and a 74-year-old phaeochromocytoma patient without MTC. Furthermore, we showed that the co-occurrence of Y791F with the strong RET C634Y mutation explains the aggressive MTC phenotypes observed in a large affected family that was initially reported as Y791F-only. Our literature review revealed that limited analyses have led to the misclassification of RET Y791F as a probable pathogenic variant and, consequently, to the occurrence of unnecessary thyroidectomies. The current study will have a substantial clinical influence, as it reveals, in a comprehensive manner, that RET Y791F only shows no association with MTC susceptibility.
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA toledorodrigo@usp.br toledorodrigo79@gmail.com.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Toledo
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Hatakana
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Delmar M
authors.initials: DM
authors.lastname: Lourenço
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Lindsey
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Cleber P
authors.initials: CP
authors.lastname: Camacho
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Marcio
authors.initials: M
authors.lastname: Almeida
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: José V
authors.initials: JV
authors.lastname: Lima
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sekiya
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Garralda
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Michel S
authors.initials: MS
authors.lastname: Naslavsky
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Guilherme L
authors.initials: GL
authors.lastname: Yamamoto
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Monize
authors.initials: M
authors.lastname: Lazar
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Osorio
authors.initials: O
authors.lastname: Meirelles
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Tiago J P
authors.initials: TJ
authors.lastname: Sobreira
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Lebrao
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Yeda A O
authors.initials: YA
authors.lastname: Duarte
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Mayana
authors.initials: M
authors.lastname: Zatz
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Janete M
authors.initials: JM
authors.lastname: Cerutti
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA.
authors.forename: Rui M B
authors.initials: RM
authors.lastname: Maciel
authors.affiliation: Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNational Institute on Aging, Bethesda, Maryland, USA Endocrine Genetics Unit (Laboratório de Investigação Médica/LIM-25) of Hospital das ClínicasUniversity of São Paulo School of Medicine, São Paulo, São Paulo 05403-010, BrazilNursing SchoolSchool of Public HealthHuman Genome Research CenterUniversity of São Paulo, São Paulo, São Paulo, BrazilDivision of GeneticsGenetic Bases of Thyroid Tumors Laboratory, Department of Morphology and GeneticsDivision of EndocrinologyLaboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, BrazilBrazilian National Laboratory of BiosciencesCampinas, São Paulo, BrazilCentro Integral Oncológico Clara CampalHospital Universitário Sanchinarro, Madrid, SpainDepartment of GeneticsTexas Biomedical Research Institute, AT&T Genomic Computing Center, San Antonio, Texas, USAEndocrinology DivisionSanta Casa Hospital, São Paulo, São Paulo, BrazilLaboratory of Epidemiology and Population SciencesNat
authors.forename: Sergio P A
authors.initials: SP
authors.lastname: Toledo
mesh_terms: D000368:Aged; D018278:Carcinoma, Neuroendocrine; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D009154:Mutation; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: MEN2; RET oncogene; genetics; medullary thyroid carcinoma; multiple endocrine neoplasias