Abstract 4144: Genetic and epidemiology characterization of head and neck cancers by targeted sequencing

Abstract

Abstract Oral and pharyngeal cancer, grouped together, is the sixth most common cancer in the world. The annual estimated incidence is around 275,000 for oral and 130,300 for pharyngeal cancers excluding nasopharynx, two-thirds of these cases occurring in developing countries. The principal objective of this work was to investigate the somatic genetic changes that influence the risk of head and neck cancer occurrence and outcome, and how they interact with environmental and host factors: HPV infection, alcohol and Smoking. We selected 205 paired samples diagnosed as head and neck SCC included in two multicenter studies in Europe and Brazil: ARCAGE, a multi center case- control study, conducted between 2002-2005 involving 10 countries across Europe and the Gencapo case- control study in the state of Sao Paulo from 2001 to 2010. Targeted sequencing was performed independently on both germline DNA and the tumor material using the PGM™ System at an average depth of 250X.Sequencing included the entire coding region of 5 of the most frequently mutated genes in Head and Neck cancer: TP53, NOTCH1, CDKN2A, CASP8, and PTEN. HPV status was achieved by capsid protein serology and DNA genotyping. Statistical tests were carried out in the R statistical programming environment or using STATA statistic software. Kaplan-Meier analysis was used to determine overall survival. Statistically significant differences in exposure status were found between both series of patients with more prevalent cases of former and current both smokers and alcohol drinkers in Brazil(p=0.001). 76% and 63% of the patients in each series had at least 1 mutation and there were no significant differences in the percentage of mutations found. Most of the mutations were found in TP53 (60%) and NOTCH1 (18%). Smoking status was significantly associated to TP53 mutations (p=0.015). Positive serology for HPV16 E6 oncoprotein was associated to Oropharyngeal tumors all of which lack TP53 mutations. When comparing the survival of patients according to the mutational profile we found a reduction in overall survival for those patients carrying mutations in TP53 (p=0.002) and CDKN2A (p=0.001). Combined molecular profiling and exposure data can be a resource to assess the role of lifestyle habits on prognosis, and will help to identify early markers of survival for head and neck cancer patients. Citation Format: Sandra Perdomo, Luciana Reis, Devasena Anantharaman, James Mckay, Paul Brennan. Genetic and epidemiology characterization of head and neck cancers by targeted sequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4144. doi:10.1158/1538-7445.AM2014-4144