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

Detalhes bibliográficos
Autor(a) principal: Cury, Sarah Santiloni [UNESP]
Data de Publicação: 2021
Outros Autores: Miranda, Priscila Mayrink de, Marchi, Fabio Albuquerque, Canto, Luisa Matos do, Chulam, Thiago Celestino, Petersen, Annabeth Høgh, Aagaard, Mads M., Pinto, Clóvis Antonio Lopes, Kowalski, Luiz Paulo, Rogatto, Silvia Regina
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.oraloncology.2021.105545
http://hdl.handle.net/11449/222521
Resumo: The 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.
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spelling Germline variants in DNA repair genes are associated with young-onset head and neck cancerCancer predispositionEarly-onset cancerOral cavity carcinomasOropharynx carcinomasRisk factorsWhole-exome sequencingThe 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.Department of Clinical Genetics University Hospital of Southern Denmark Vejle Institute of Regional Health Research University of Southern DenmarkDepartment of Structural and Functional Biology São Paulo State University (UNESP)International Research Center CIPE – A.C.Camargo Cancer CenterDepartment of Head and Neck Surgery and Otorhinolaryngology A.C.Camargo Cancer CenterDepartment of Pathology A.C.Camargo Cancer CenterDepartment of Structural and Functional Biology São Paulo State University (UNESP)University of Southern DenmarkUniversidade Estadual Paulista (UNESP)CIPE – A.C.Camargo Cancer CenterA.C.Camargo Cancer CenterCury, Sarah Santiloni [UNESP]Miranda, Priscila Mayrink deMarchi, Fabio AlbuquerqueCanto, Luisa Matos doChulam, Thiago CelestinoPetersen, Annabeth HøghAagaard, Mads M.Pinto, Clóvis Antonio LopesKowalski, Luiz PauloRogatto, Silvia Regina2022-04-28T19:45:14Z2022-04-28T19:45:14Z2021-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.oraloncology.2021.105545Oral Oncology, v. 122.1879-05931368-8375http://hdl.handle.net/11449/22252110.1016/j.oraloncology.2021.1055452-s2.0-85115971702Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengOral Oncologyinfo:eu-repo/semantics/openAccess2022-04-28T19:45:14Zoai:repositorio.unesp.br:11449/222521Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T18:23:35.212525Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Germline variants in DNA repair genes are associated with young-onset head and neck cancer
title Germline variants in DNA repair genes are associated with young-onset head and neck cancer
spellingShingle Germline variants in DNA repair genes are associated with young-onset head and neck cancer
Cury, Sarah Santiloni [UNESP]
Cancer predisposition
Early-onset cancer
Oral cavity carcinomas
Oropharynx carcinomas
Risk factors
Whole-exome sequencing
title_short Germline variants in DNA repair genes are associated with young-onset head and neck cancer
title_full Germline variants in DNA repair genes are associated with young-onset head and neck cancer
title_fullStr Germline variants in DNA repair genes are associated with young-onset head and neck cancer
title_full_unstemmed Germline variants in DNA repair genes are associated with young-onset head and neck cancer
title_sort Germline variants in DNA repair genes are associated with young-onset head and neck cancer
author Cury, Sarah Santiloni [UNESP]
author_facet Cury, Sarah Santiloni [UNESP]
Miranda, Priscila Mayrink de
Marchi, Fabio Albuquerque
Canto, Luisa Matos do
Chulam, Thiago Celestino
Petersen, Annabeth Høgh
Aagaard, Mads M.
Pinto, Clóvis Antonio Lopes
Kowalski, Luiz Paulo
Rogatto, Silvia Regina
author_role author
author2 Miranda, Priscila Mayrink de
Marchi, Fabio Albuquerque
Canto, Luisa Matos do
Chulam, Thiago Celestino
Petersen, Annabeth Høgh
Aagaard, Mads M.
Pinto, Clóvis Antonio Lopes
Kowalski, Luiz Paulo
Rogatto, Silvia Regina
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv University of Southern Denmark
Universidade Estadual Paulista (UNESP)
CIPE – A.C.Camargo Cancer Center
A.C.Camargo Cancer Center
dc.contributor.author.fl_str_mv Cury, Sarah Santiloni [UNESP]
Miranda, Priscila Mayrink de
Marchi, Fabio Albuquerque
Canto, Luisa Matos do
Chulam, Thiago Celestino
Petersen, Annabeth Høgh
Aagaard, Mads M.
Pinto, Clóvis Antonio Lopes
Kowalski, Luiz Paulo
Rogatto, Silvia Regina
dc.subject.por.fl_str_mv Cancer predisposition
Early-onset cancer
Oral cavity carcinomas
Oropharynx carcinomas
Risk factors
Whole-exome sequencing
topic Cancer predisposition
Early-onset cancer
Oral cavity carcinomas
Oropharynx carcinomas
Risk factors
Whole-exome sequencing
description The 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.
publishDate 2021
dc.date.none.fl_str_mv 2021-11-01
2022-04-28T19:45:14Z
2022-04-28T19:45:14Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.oraloncology.2021.105545
Oral Oncology, v. 122.
1879-0593
1368-8375
http://hdl.handle.net/11449/222521
10.1016/j.oraloncology.2021.105545
2-s2.0-85115971702
url http://dx.doi.org/10.1016/j.oraloncology.2021.105545
http://hdl.handle.net/11449/222521
identifier_str_mv Oral Oncology, v. 122.
1879-0593
1368-8375
10.1016/j.oraloncology.2021.105545
2-s2.0-85115971702
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Oral Oncology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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