Germline variants in DNA repair genes are associated with young-onset head and neck cancer
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , |
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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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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1808128926260658176 |