Screening of genomic alterations in head and neck carcinomas of young patients by total exome sequencing

Abstract

Squamous cell carcinoma (SCC) is the most common disease of the head and neck (HN), being the eighth cause of cancer death in the world. The most important risk factors described for SCCHN are the alcohol consumption and smoking habit, in addition to human papillomavirus infection. A group of SCCHN patients aged under 45 years is characterized by the most severe form of the disease and are not associated with the classical risk factors described for the development of the disease. There is no consensus in the literature regarding the etiology, clinical course and prognosis of SCCHN in young patients. Besides its clinical importance, studies with this group of tumors are rare, mainly focusing on molecular aspects related to disease development and progression. Recent exome sequencing methods have been used to identify mutations and genome variations. Cheaper and faster than the traditional genome mapping, this technique has the potential to identify genes responsible for rare syndromes, which are undiagnosed or with inaccurate diagnosis. Thus, this study aims to sequence the whole exome of young patients (d 45 years) with SCCHN, particularly oral and oropharyngeal carcinomas, aiming to identify genetic alterations associated with the tumor development. The paired analysis comparing DNA from tumor and peripheral blood will be conducted in two groups of patients using two different sequencing strategies: in the first strategy the whole genome will be sequenced and in the second enriched altered regions will be evaluated. This study can potentially identify genomic alterations associated with the tumor development in young patients and contribute to delineate targeted therapies for these patients. (AU)