Germline variants in DNA repair genes are associated with young-onset head and neck cancer

Registro completo de metadados
MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversity of Southern Denmark-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorCIPE – A.C.Camargo Cancer Center-
Autor(es): dc.contributorA.C.Camargo Cancer Center-
Autor(es): dc.creatorCury, Sarah Santiloni-
Autor(es): dc.creatorMiranda, Priscila Mayrink de-
Autor(es): dc.creatorMarchi, Fabio Albuquerque-
Autor(es): dc.creatorCanto, Luisa Matos do-
Autor(es): dc.creatorChulam, Thiago Celestino-
Autor(es): dc.creatorPetersen, Annabeth Høgh-
Autor(es): dc.creatorAagaard, Mads M.-
Autor(es): dc.creatorPinto, Clóvis Antonio Lopes-
Autor(es): dc.creatorKowalski, Luiz Paulo-
Autor(es): dc.creatorRogatto, Silvia Regina-
Data de aceite: dc.date.accessioned2025-08-21T18:52:46Z-
Data de disponibilização: dc.date.available2025-08-21T18:52:46Z-
Data de envio: dc.date.issued2022-04-28-
Data de envio: dc.date.issued2022-04-28-
Data de envio: dc.date.issued2021-10-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.oraloncology.2021.105545-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/222521-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/222521-
Descrição: dc.descriptionThe genetic predisposition to head and neck carcinomas (HNSCC) and how the known risk factors (papillomavirus infection, alcohol, and tobacco consumption) contribute to the early-onset disease are barely explored. Although HNSCC at early onset is rare, its frequency is increasing in recent years. Germline and somatic variants were assessed to build a comprehensive genetic influence pattern in HNSCC predisposition and patient outcome. Whole-exome sequencing was performed in 45 oral and oropharynx carcinomas paired with normal samples of young adults (≤49 years). We found FANCG, CDKN2A, and TPP germline variants previously associated with HNSCC risk. At least one germline variant in DNA repair pathway genes was detected in 67% of cases. Germline and somatic variants (including copy number variations) in FAT1 gene were identified in 9 patients (20%) and 12 tumors (30%), respectively. Somatic variants were found in HNSCC associated genes, such as TP53, CDKN2A, and PIK3CA. To date, 55 of 521 cases from the large cohort of TCGA presented < 49 years old. A comparison between the somatic alterations of TCGA-HNSCC at early onset and our dataset revealed strong similarities. Protein-protein interaction analysis between somatic and germline altered genes revealed a central role of TP53. Altogether, germline alterations in DNA repair genes potentially contribute to an increased risk of developing HNSCC at early-onset, while FAT1 could impact the prognosis.-
Descrição: dc.descriptionDepartment of Clinical Genetics University Hospital of Southern Denmark Vejle Institute of Regional Health Research University of Southern Denmark-
Descrição: dc.descriptionDepartment of Structural and Functional Biology São Paulo State University (UNESP)-
Descrição: dc.descriptionInternational Research Center CIPE – A.C.Camargo Cancer Center-
Descrição: dc.descriptionDepartment of Head and Neck Surgery and Otorhinolaryngology A.C.Camargo Cancer Center-
Descrição: dc.descriptionDepartment of Pathology A.C.Camargo Cancer Center-
Descrição: dc.descriptionDepartment of Structural and Functional Biology São Paulo State University (UNESP)-
Idioma: dc.languageen-
Relação: dc.relationOral Oncology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectCancer predisposition-
Palavras-chave: dc.subjectEarly-onset cancer-
Palavras-chave: dc.subjectOral cavity carcinomas-
Palavras-chave: dc.subjectOropharynx carcinomas-
Palavras-chave: dc.subjectRisk factors-
Palavras-chave: dc.subjectWhole-exome sequencing-
Título: dc.titleGermline variants in DNA repair genes are associated with young-onset head and neck cancer-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

Não existem arquivos associados a este item.