38. Retrotransposon activity in young patients with oral Squamous Cell Carcinoma (OSCC)

Abstract

Background: A recent alarming increase in the incidence of OSCC has been seen in young patients in the absence of tobacco or alcohol use, or HPV integration. Retrotransposons are mobile DNA elements which have been shown to have a role in cancer, particularly LINE-1, with transposition events resulting in mutagenesis. Aims: To compare the activity of three retrotransposon families (LINE-1, SVA and Alu) between young (<45) and older patients with OSCC. Methods: 7 young and 16 older non-HPV OSCC patients, whose genomes were sequenced at high depth, were identified from The Cancer Genome Atlas (TCGA). The Mobile Element Locator Tool (MELT) was employed to detect non-reference retrotransposon events in the selected genomes. Results and conclusions: The total count of putative somatic LINE-1 insertions was significantly higher in the young as compared to the older cohort (p=0.004). A significantly higher number of these events were found to occur close to genes (p=0.019), with possible roles in cancer predisposition syndromes (e.g., OR4C45 and DTNB). RNA-Seq data is being analysed to assess the potential impact of the insertions on gene expression. The presence of elevated somatic LINE-1 activity in young patients may shed light on the increasing development of OSCC at an early age.