Germline mutation in mus81 resulting in impaired protein stability is associated with familial breast and thyroid cancer

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorA.C. Camargo Cancer Center-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorVejle University Hospital-
Autor(es): dc.contributorUnB-
Autor(es): dc.contributorUniversity of Toronto-
Autor(es): dc.contributorSlovak Academy of Sciences-
Autor(es): dc.contributorHospital Sirio Libanês-
Autor(es): dc.contributorUniversity of Southern Denmark-
Autor(es): dc.creatorPinheiro, Maisa [UNESP]-
Autor(es): dc.creatorLupinacci, Fernanda Cristina Sulla-
Autor(es): dc.creatorSantiago, Karina Miranda-
Autor(es): dc.creatorDrigo, Sandra Aparecida [UNESP]-
Autor(es): dc.creatorMarchi, Fabio Albuquerque-
Autor(es): dc.creatorFonseca-Alves, Carlos Eduardo [UNESP]-
Autor(es): dc.creatorAndrade, Sonia Cristina da Silva-
Autor(es): dc.creatorAagaard, Mads Malik-
Autor(es): dc.creatorBasso, Tatiane Ramos-
Autor(es): dc.creatorReis, Mariana Bisarro Dos-
Autor(es): dc.creatorVillacis, Rolando André Rios-
Autor(es): dc.creatorRoffé, Martin-
Autor(es): dc.creatorHajj, Glaucia Noeli Maroso-
Autor(es): dc.creatorJurisica, Igor-
Autor(es): dc.creatorKowalski, Luiz Paulo-
Autor(es): dc.creatorAchatz, Maria Isabel-
Autor(es): dc.creatorRogatto, Silvia Regina-
Data de aceite: dc.date.accessioned2022-02-22T00:30:56Z-
Data de disponibilização: dc.date.available2022-02-22T00:30:56Z-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-05-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/cancers12051289-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/200526-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/200526-
Descrição: dc.descriptionMultiple primary thyroid cancer (TC) and breast cancer (BC) are commonly diagnosed, and the lifetime risk for these cancers is increased in patients with a positive family history of both TC and BC. Although this phenotype is partially explained by TP53 or PTEN mutations, a significant number of patients are negative for these alterations. We judiciously recruited patients diagnosed with BC and/or TC having a family history of these tumors and assessed their whole-exome sequencing. After variant prioritization, we selected MUS81 c.1292G>A (p.R431H) for further investigation. This variant was genotyped in a healthy population and sporadic BC/TC tissues and investigated at the protein level and cellular models. MUS81 c.1292G>A was the most frequent variant (25%) and the strongest candidate due to its function of double-strand break repair. This variant was confirmed in four relatives from two families. MUS81 p.R431H protein exhibited lower expression levels in tumors from patients positive for the germline variant, compared with wild-type BC, and normal breast and thyroid tissues. Using cell line models, we showed that c.1292G>A induced protein instability and affected DNA damage response. We suggest that MUS81 is a novel candidate involved in familial BC/TC based on its low frequency in healthy individuals and proven effect in protein stability.-
Descrição: dc.descriptionSyddansk Universitet-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionFaculty of Medicine Sao Paulo State University UNESP-
Descrição: dc.descriptionInternational Research Center A.C. Camargo Cancer Center-
Descrição: dc.descriptionDepartment of Surgery and Orthopedics Experimental Research Unity Faculty of Medicine São Paulo State University UNESP-
Descrição: dc.descriptionDepartment of Veterinary Surgery and Anesthesiology São Paulo State University UNESP-
Descrição: dc.descriptionDepartment of Genetics and Evolutionary Biology University of São Paulo USP-
Descrição: dc.descriptionDepartment of Clinical Genetics Vejle University Hospital-
Descrição: dc.descriptionDepartment of Genetics and Morphology Institute of Biological Sciences University of Brasília UnB, DF-
Descrição: dc.descriptionKrembil Research Institute UHN University of Toronto-
Descrição: dc.descriptionInstitute of Neuroimmunology Slovak Academy of Sciences-
Descrição: dc.descriptionCancer Genetics Unit Centro de Oncologia Hospital Sirio Libanês-
Descrição: dc.descriptionDepartment of Clinical Genetics Vejle University Hospital Institute of Regional Health Research University of Southern Denmark-
Descrição: dc.descriptionFaculty of Medicine Sao Paulo State University UNESP-
Descrição: dc.descriptionDepartment of Surgery and Orthopedics Experimental Research Unity Faculty of Medicine São Paulo State University UNESP-
Descrição: dc.descriptionDepartment of Veterinary Surgery and Anesthesiology São Paulo State University UNESP-
Descrição: dc.descriptionFAPESP: 2012/12714-5-
Descrição: dc.descriptionFAPESP: 2013/0186-7-
Descrição: dc.descriptionFAPESP: 2014/03983-8-
Descrição: dc.descriptionCNPq: 481132/2012-0-
Descrição: dc.descriptionCAPES: PDSE 8195/14-5-
Idioma: dc.languageen-
Relação: dc.relationCancers-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectBreast cancer-
Palavras-chave: dc.subjectExome sequencing-
Palavras-chave: dc.subjectFamilial cancer-
Palavras-chave: dc.subjectFunctional analysis-
Palavras-chave: dc.subjectMUS81-
Palavras-chave: dc.subjectThyroid cancer-
Título: dc.titleGermline mutation in mus81 resulting in impaired protein stability is associated with familial breast and thyroid cancer-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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