| Texto completo | |
| Autor(es): |
Cury, Sarah Santiloni
[1, 2]
;
de Miranda, Priscila Mayrink
[3]
;
Marchi, Fabio Albuquerque
[3]
;
do Canto, Luisa Matos
[1]
;
Chulam, Thiago Celestino
[4]
;
Petersen, Annabeth Hogh
[1]
;
Aagaard, Mads M.
[1]
;
Pinto, Clovis Antonio Lopes
[5]
;
Kowalski, Luiz Paulo
[4]
;
Rogatto, Silvia Regina
[1]
Número total de Autores: 10
|
| Afiliação do(s) autor(es): | [1] Univ Southern Denmark, Dept Clin Genet, Univ Hosp Southern Denmark, Inst Reg Hlth Res, Odense - Denmark
[2] Sao Paulo State Univ UNESP, Dept Struct & Funct Biol, Botucatu, SP - Brazil
[3] CIPE AC Camargo Canc Ctr, Int Res Ctr, Sao Paulo - Brazil
[4] AC Camargo Canc Ctr, Dept Head & Neck Surg & Otorhinolaryngol, Sao Paulo - Brazil
[5] AC Camargo Canc Ctr, Dept Pathol, Sao Paulo - Brazil
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Oral Oncology; v. 122, NOV 2021. |
| Citações Web of Science: | 0 |
| 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 FATI 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 FATI could impact the prognosis. (AU) | |
| Processo FAPESP: | 08/57887-9 - Instituto Nacional de Oncogenômica |
| Beneficiário: | Luiz Paulo Kowalski |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |