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

Autor: Cury SS; Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle, Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark; Department of Structural and Functional Biology, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil., Miranda PM; International Research Center, CIPE - A.C.Camargo Cancer Center, São Paulo, Brazil., Marchi FA; International Research Center, CIPE - A.C.Camargo Cancer Center, São Paulo, Brazil., Canto LMD; Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle, Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark., Chulam TC; Department of Head and Neck Surgery and Otorhinolaryngology, A.C.Camargo Cancer Center, São Paulo, Brazil., Petersen AH; Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle, Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark., Aagaard MM; Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle, Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark., Pinto CAL; Department of Pathology, A.C.Camargo Cancer Center, São Paulo, Brazil., Kowalski LP; Department of Head and Neck Surgery and Otorhinolaryngology, A.C.Camargo Cancer Center, São Paulo, Brazil., Rogatto SR; Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle, Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark. Electronic address: silvia.regina.rogatto@rsyd.dk.
Jazyk: angličtina
Zdroj: Oral oncology [Oral Oncol] 2021 Nov; Vol. 122, pp. 105545. Date of Electronic Publication: 2021 Sep 28.
DOI: 10.1016/j.oraloncology.2021.105545
Abstrakt: 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.
(Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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