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

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dc.contributor.authorCury, Sarah Santiloni [UNESP]
dc.contributor.authorMiranda, Priscila Mayrink de
dc.contributor.authorMarchi, Fabio Albuquerque
dc.contributor.authorCanto, Luisa Matos do
dc.contributor.authorChulam, Thiago Celestino
dc.contributor.authorPetersen, Annabeth Høgh
dc.contributor.authorAagaard, Mads M.
dc.contributor.authorPinto, Clóvis Antonio Lopes
dc.contributor.authorKowalski, Luiz Paulo
dc.contributor.authorRogatto, Silvia Regina
dc.contributor.institutionUniversity of Southern Denmark
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionCIPE – A.C.Camargo Cancer Center
dc.contributor.institutionA.C.Camargo Cancer Center
dc.date.accessioned2022-04-28T19:45:14Z
dc.date.available2022-04-28T19:45:14Z
dc.date.issued2021-11-01
dc.description.abstractThe 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.en
dc.description.affiliationDepartment of Clinical Genetics University Hospital of Southern Denmark Vejle Institute of Regional Health Research University of Southern Denmark
dc.description.affiliationDepartment of Structural and Functional Biology São Paulo State University (UNESP)
dc.description.affiliationInternational Research Center CIPE – A.C.Camargo Cancer Center
dc.description.affiliationDepartment of Head and Neck Surgery and Otorhinolaryngology A.C.Camargo Cancer Center
dc.description.affiliationDepartment of Pathology A.C.Camargo Cancer Center
dc.description.affiliationUnespDepartment of Structural and Functional Biology São Paulo State University (UNESP)
dc.identifierhttp://dx.doi.org/10.1016/j.oraloncology.2021.105545
dc.identifier.citationOral Oncology, v. 122.
dc.identifier.doi10.1016/j.oraloncology.2021.105545
dc.identifier.issn1879-0593
dc.identifier.issn1368-8375
dc.identifier.scopus2-s2.0-85115971702
dc.identifier.urihttp://hdl.handle.net/11449/222521
dc.language.isoeng
dc.relation.ispartofOral Oncology
dc.sourceScopus
dc.subjectCancer predisposition
dc.subjectEarly-onset cancer
dc.subjectOral cavity carcinomas
dc.subjectOropharynx carcinomas
dc.subjectRisk factors
dc.subjectWhole-exome sequencing
dc.titleGermline variants in DNA repair genes are associated with young-onset head and neck canceren
dc.typeArtigo

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