ArticleEndocrine-related cancer2015
Comprehensive assessment of the disputed RET Y791F variant shows no association with medullary thyroid carcinoma susceptibility.
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Article in Endocrine-related cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23citing papers in PubMed
3.6field-weighted citation impact, top 7% of its field
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- Variability in proliferative and migratory defects in Hirschsprung disease-associated RET pathogenic variants.American journal of human genetics · 2025Article
- Hereditary Medullary Thyroid Cancer: Genotype-Phenotype Correlation.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2025Review
- Article
- Variability in proliferative and migratory defects in Hirschsprung disease-associatedbioRxiv : the preprint server for biology · 2024Article
- Association of the Genomic Profile of Medullary Thyroid Carcinoma with Tumor Characteristics and Clinical Outcomes in an International Multicenter Study.Thyroid : official journal of the American Thyroid Association · 2024Article
- Article
- RET Proto-Oncogene Variants in Patients with Medullary Thyroid Carcinoma from the Mediterranean Basin: A Brief Report.Life (Basel, Switzerland) · 2023Article
- Distribution of RET proto-oncogene variants in children with appendicitis.Molecular genetics & genomic medicine · 2022Article
- Analytical Performance of NGS-Based Molecular Genetic Tests Used in the Diagnostic Workflow of Pheochromocytoma/Paraganglioma.Cancers · 2021Article
- Spectrum of Germline RET variants identified by targeted sequencing and associated Multiple Endocrine Neoplasia type 2 susceptibility in China.BMC cancer · 2021Article
- Results and Clinical Interpretation of GermlineCancers · 2020Article
- The synergy of germline C634Y and V292M RET mutations in a northern Chinese family with multiple endocrine neoplasia type 2A.Journal of cellular and molecular medicine · 2020Article
- Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study.Endocrine connections · 2019Article
- A pioneering RET genetic screening study in the State of Ceará, Brazil, evaluating patients with medullary thyroid cancer and at-risk relatives: experience with 247 individuals.Archives of endocrinology and metabolism · 2018Article
- Incidence and prevalence of multiple endocrine neoplasia 2A in Denmark 1901-2014: a nationwide study.Clinical epidemiology · 2018Article
- NGS based identification of mutational hotspots for targeted therapy in anaplastic thyroid carcinoma.Oncotarget · 2017Article
- Distribution of RET Mutations in Multiple Endocrine Neoplasia 2 in Denmark 1994-2014: A Nationwide Study.Thyroid : official journal of the American Thyroid Association · 2017Article
- Medullary Thyroid Carcinoma Associated with Germline RETThyroid : official journal of the American Thyroid Association · 2016Article
- Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.American journal of human genetics · 2016Article
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Authors and funding
21 authors at 7 institutions in 3 countries.
Rodrigo A ToledoEndocrine 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.
Roxanne HatakanaEndocrine 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.
Delmar M LourençoEndocrine 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.
Susan C LindseyEndocrine 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.
Cleber P CamachoEndocrine 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.
Marcio AlmeidaEndocrine 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.
José V LimaEndocrine 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.
Tomoko SekiyaEndocrine 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.
Elena GarraldaEndocrine 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.
Michel S NaslavskyEndocrine 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.
Guilherme L YamamotoEndocrine 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.
Monize LazarEndocrine 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.
Osorio MeirellesEndocrine 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.
Tiago J P SobreiraEndocrine 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.
Maria Lucia LebraoEndocrine 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.
Yeda A O DuarteEndocrine 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.
John BlangeroEndocrine 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.
Mayana ZatzEndocrine 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.
Janete M CeruttiEndocrine 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.
Rui M B MacielEndocrine 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.
Sergio P A ToledoEndocrine 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
Hospital São Paulo · BRUniversidade de São Paulo · BRUniversidade Federal de São Paulo · BRAT&T (United States) · USBrazilian Biosciences National Laboratory · BRHospital Universitario HM Sanchinarro · ESNational Institutes of Health · US
Funding
No grant is acknowledged in the PubMed record.
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.
Indexed as
AgedCarcinoma, NeuroendocrineCase-Control StudiesCohort StudiesFemaleGene FrequencyGenetic Predisposition to DiseaseGenotypeGerm-Line MutationHumansMaleMutationProto-Oncogene MasProto-Oncogene Proteins c-retThyroid NeoplasmsMAS1 protein, humanProto-Oncogene MasProto-Oncogene Proteins c-retRET protein, humangeneticsmedullary thyroid carcinomaMEN2multiple endocrine neoplasiasRET oncogene
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