Author(s): 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
Date: 2022
Persistent ID: http://hdl.handle.net/11449/222521
Origin: Oasisbr
Subject(s): Cancer predisposition; Early-onset cancer; Oral cavity carcinomas; Oropharynx carcinomas; Risk factors; Whole-exome sequencing
Made available in DSpace on 2022-04-28T19:45:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-01
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.
Department of Clinical Genetics University Hospital of Southern Denmark Vejle Institute of Regional Health Research University of Southern Denmark
Department of Structural and Functional Biology São Paulo State University (UNESP)
International Research Center CIPE – A.C.Camargo Cancer Center
Department of Head and Neck Surgery and Otorhinolaryngology A.C.Camargo Cancer Center
Department of Pathology A.C.Camargo Cancer Center
Department of Structural and Functional Biology São Paulo State University (UNESP)
