title: Association between the p27 rs2066827 variant and tumor multiplicity in patients harboring MEN1 germline mutations.
abstract: OBJECTIVE
  To date, no evidence of robust genotype-phenotype correlation or disease modifiers for multiple endocrine neoplasia type 1 (MEN1) syndrome has been described, leaving the highly variable clinical presentation of patients unaccounted for.
  
  
  METHODS
  As the CDKN1B (p27) gene causes MEN4 syndrome and it is transcriptionally regulated by the product of the MEN1 gene (menin), we sought to analyze whether p27 influences the phenotype of MEN1-mutated patients. The cohort consisted of 100 patients carrying germline MEN1 gene mutations and 855 population-matched control individuals.
  
  
  METHODS
  Genotyping of the coding p27 c.326T>G (V109G) variant was performed by sequencing and restriction site digestion, and the genotypes were associated with clinical parameters by calculating odds ratios (ORs) and their 95% CIs using logistic regression.
  
  
  RESULTS
  There were significant differences in p27 V109G allele frequencies between controls and MEN1-mutated patients (OR=2.55, P=0.019, CI=1.013-5.76). Among patients who are ≥30 years old carrying truncating MEN1 mutations, the T allele was strongly associated with susceptibility to tumors in multiple glands (three to four glands affected vs one to two glands affected; OR=18.33; P=0.002, CI=2.88-16.41). This finding remained significant after the Bonferroni's multiple testing correction, indicating a robust association. No correlations were observed with the development of MEN1-related tumors such as hyperparathyroidism, pituitary adenomas, and enteropancreatic and adrenocortical tumors.
  
  
  CONCLUSIONS
  Our study suggests that the p27 tumor suppressor gene acts as a disease modifier for the MEN1 syndrome associated with MEN1 germline mutations. If confirmed in independent patient cohorts, this finding could facilitate the management of this clinically complex disease.
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Viviane C
authors.initials: VC
authors.lastname: Longuini
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Delmar M
authors.initials: DM
authors.lastname: Lourenço
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sekiya
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Osorio
authors.initials: O
authors.lastname: Meirelles
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Tatiana D
authors.initials: TD
authors.lastname: Goncalves
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Flavia L
authors.initials: FL
authors.lastname: Coutinho
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Francisco
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Luciana H
authors.initials: LH
authors.lastname: Osaki
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Venancio A F
authors.initials: VA
authors.lastname: Alves
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Sheila A C
authors.initials: SA
authors.lastname: Siqueira
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, BrazilEndocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: David
authors.initials: D
authors.lastname: Schlesinger
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Michel S
authors.initials: MS
authors.lastname: Naslavsky
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Mayana
authors.initials: M
authors.lastname: Zatz
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Yeda A O
authors.initials: YA
authors.lastname: Duarte
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Lebrão
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gama
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Misu
authors.initials: M
authors.lastname: Lee
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Sara
authors.initials: S
authors.lastname: Molatore
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Maria Adelaide A
authors.initials: MA
authors.lastname: Pereira
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Raquel S
authors.initials: RS
authors.lastname: Jallad
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Marcello D
authors.initials: MD
authors.lastname: Bronstein
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Malebranche B
authors.initials: MB
authors.lastname: Cunha-Neto
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Liberman
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Maria Candida B V
authors.initials: MC
authors.lastname: Fragoso
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, BrazilEndocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Sergio P A
authors.initials: SP
authors.lastname: Toledo
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Pellegata
authors.affiliation: Endocrine Genetics Unit (Laboratorio de Investigacao Medica/LIM-25)Neuroendocrinology UnitNeuroendocrinology-Neurosurgery UnitAdrenal Unit (LIM-42)General Endocrinology UnitExperimental Oncology Laboratory (LIM-24)Department of PathologyNursing SchoolSchool of Public Health of Hospital das ClínicasUniversity of Sao Paulo School of Medicine, Sao Paulo, BrazilBrigadeiro HospitalSao Paulo, BrazilHuman Genome Research CenterUniversity of Sao Paulo, Sao Paulo, BrazilInstituto do CérebroInstituto Israelita de Ensino e Pesquisa Albert Einstein, Sao Paulo, BrazilNational Institute of AgingNational Institutes of Health (NIH), Bethesda, Maryland, USAInstitute of PathologyHelmholtz Zentrum München, Neuherberg, GermanyInstitute of Biomedical SciencesUniversity of Sao Paulo, Sao Paulo, BrazilDivision of EndocrinologyFederal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil toledorodrigo@usp.br toledorodrigo79@gmail.com.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Toledo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000175:diagnosis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27