Tracking Genomic Alterations In Young Patients With Head And Neck Carcinomas Using Whole-Exome Sequencing

Abstract Head and neck squamous cell carcinomas (HNSCC) often affect patients over 60 years, although epidemiological studies have shown an increased incidence in young adults (18-45 years), especially those having oropharynx and oral cavity tumors. There is no consensus regarding the etiology, clinical course and prognosis of HNSCC in young patients that often do not have the risk factors frequently described as associated with the disease (alcohol consumption, smoking and HPV infection). Despite its importance, studies with this group of patients are scarce, mainly focusing on the molecular aspects involved in the development and progression of the disease. In this study, we evaluated 36-paired samples (6 oral cavity, 12 oropharyngeal carcinomas and 18 matched blood samples) by whole exome sequencing (WES) aiming to identify molecular markers useful to clinical practice. Libraries were prepared (Illumina Nextera exome Enrichment kit) for WES using the high quality DNA from tumor tissue and peripheral blood of each patient (HiSeq2500, Illumina). The coverage reached an average of 55x per sample. We used an in-house pipeline for cleaning, mapping and SNP calling revealing an average of 36,494 SNPs per sample. A paired comparison of normal and tumor samples was performed considering only the exclusive variants in tumors, after exclusion of the common variants, based on 1000 Genomes (http://www.1000genomes.org/), project and 6500 exomes (evs.gs.washington.edu/). It was identified 248 variants distributed in 169 genes, with 184 (74%) classified as new (variant not described) and 64 (26%) as rare (population frequency ≤0.1%). Three genes, ZNF717, HYDIN and KCNJ12, presented higher frequency of SNPs and were enriched to head and neck carcinoma (p = 1,9×10-9) and calcium (p = 1.82×10-3) pathways. Considering only tongue samples (4 cases) from non-smokers and HPV negative patients, the ZNF717 and HYDIN genes remained among those with the highest frequency of SNPs [non-smokers: HYDIN (23 SNPs) and ZNF77 (24 SNPs); HPV-negative: HYDIN (6 SNPs) and ZNF77 (5 SNPs)]. These genes are putative drivers in young patients with HNSCC. Financial Support: FAPESP (2013/06897-2) and INCiTO (FAPESP: 2008/57887-9 and CNPq 573589/08-9) Citation Format: Priscila Mayrink Miranda, Fabio A. Marchi, Maísa Pinheiro, Luiz Paulo Kowalski, Silvia Regina Rogatto. Tracking genomic alterations in young patients with head and neck carcinomas using whole-exome sequencing. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4915. doi:10.1158/1538-7445.AM2015-4915