Impact of genetic variants in clinical outcome of a cohort of patients with oropharyngeal squamous cell carcinoma

Author(s):Show less -

de Carvalho, Ana Carolina ^[1] ; Perdomo, Sandra ^{[2, 3]} ; dos Santos, Wellington ^[1] ; Fernandes, Gabriela Carvalho ^[4] ; de Jesus, Lais Machado ^[1] ; Carvalho, Raiany Santos ^[5] ; Scapulatempo-Neto, Cristovam ^{[1, 6]} ; de Almeida, Gisele Caravina ^[5] ; Sorroche, Bruna Pereira ^[1] ; Batista Arantes, Lidia Maria Rebolho ^[1] ; Melendez, Matias Eliseo ^{[1, 7, 8]} ; De Marchi, Pedro ^{[9, 10]} ; Hayes, Neil ^[11] ; Reis, Rui Manuel ^{[12, 1, 13]} ; Carvalho, Andre Lopes ^{[1, 2]}

Affiliation:Show less -

^[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, SP - Brazil

^[2] Int Agcy Res Canc, Lyon - France

^[3] Univ El Bosque, Fac Med, Inst Nutr Genet & Metab Res, Bogota - Colombia

^[4] Barretos Canc Hosp, Ctr Mol Diag, Barretos, SP - Brazil

^[5] Barretos Canc Hosp, Res Support Ctr, Barretos, SP - Brazil

^[6] Diagnost Amer DASA, Pathol & Mol Diagnost Serv, Sao Paulo, SP - Brazil

^[7] Pele Little Prince Res Inst, Curitiba, Parana - Brazil

^[8] Little Prince Coll, Curitiba, Parana - Brazil

^[9] Barretos Canc Hosp, Dept Med Oncol, Barretos, SP - Brazil

^[10] Oncoclinicas, Rio De Janeiro, RJ - Brazil

^[11] Univ Tennessee, Hlth Sci Ctr, UTHSC Ctr Canc Res, Dept Med, Div Oncol, Memphis, TN - USA

^[12] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal

^[13] Univ Minho, Med Sch, Life & Hlth Sci Res Inst ICVS, Braga - Portugal

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 JUN 19 2020.
• Web of Science Citations: 0

Abstract

Tobacco- or human papillomavirus- driven oropharyngeal squamous cell carcinomas (OpSCC) represent distinct clinical, biological and epidemiological entities. The aim of this study was to identify genetic variants based on somatic alterations in OpSCC samples from an admixed population, and to test for association with clinical features. The entire coding region of 15 OpSCC driver genes was sequenced by next-generation sequencing in 51 OpSCC FFPE samples. Thirty-five percent of the patients (18/51) were HPV-positive and current or past tobacco consumption was reported in 86.3% (44/51). The mutation profile identified an average of 2.67 variants per sample. Sixty-three percent of patients (32/51; 62.7%) were mutated for at least one of the genes tested and TP53 was the most frequently mutated gene. The presence of mutation in NOTCH1 and PTEN, significantly decreased patient's recurrence-free survival, but only NOTCH1 mutation remained significant after stepwise selection, with a risk of recurrence of 4.5 (HR 95% CI=1.11-14.57; Cox Regression p=0.034). These results show that Brazilian OpSCC patients exhibit a similar clinical and genetic profile in comparison to other populations. Molecular characterization is a promising tool for the definition of clinical subgroups, aiding in a more precise tailoring of treatment and prognostication. (AU)

• FAPESP's process: 15/01286-0 - Characterization of genetic and epigenetic alterations in specific genes in HPV-positive and HPV-negative tumors of patients with head and neck squamous cell carcinoma
• Grantee: André Lopes Carvalho
• Support Opportunities: Regular Research Grants