Abstract 3931: Whole genome and whole exome sequencing of head and neck cancer

Abstract

Abstract Head and neck cancer is responsible for an enormous cancer burden worldwide, with an estimated 500,000 new cases per year. However, knowledge of the spectrum of genetic alterations that drive this malignancy remains incomplete. Previous studies of this disease have identified recurrent somatic mutations in a few specific genes, but few systematic genome-scale studies have been performed. Accordingly, we have undertaken a pilot study of complete genome/exome characterization in this malignancy. We obtained genomic DNA from 40 head and neck tumors together with matched normal DNA from whole blood. To date, we have obtained whole exome sequencing of 28 tumor/normal pairs and whole genome sequencing of two tumor/normal pairs. The average base mutation rate is 3.1 × 10-6 (range = 2.9 × 10-7 to 8.8 × 10-6), consistent with rates observed in lung cancer and other tobacco-related malignancies. We also identified 24 high-confidence somatic rearrangements in one sample and 120 in the other sample (including 7 and 44 inter-chromosomal rearrangements, respectively). In addition to frequent mutations of TP53 (53%), HRAS, PIK3CA, and PTEN, we also observed other recurrently mutated genes that implicate several oncogenic pathways. Furthermore, layering of somatic mutation data onto known pathway information strengthens the evidence for several oncogenic processes not previously implicated in head and neck cancer. Altogether, these data should enhance our understanding of the mechanisms that drive head and neck carcinogenesis and progression and may also illuminate new therapeutic opportunities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3931. doi:10.1158/1538-7445.AM2011-3931