Cury, 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 Regina2022-04-282022-04-282021-11-01Oral Oncology, v. 122.1879-05931368-8375http://hdl.handle.net/11449/222521The 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.engCancer predispositionEarly-onset cancerOral cavity carcinomasOropharynx carcinomasRisk factorsWhole-exome sequencingArtigo10.1016/j.oraloncology.2021.1055452-s2.0-85115971702