RetroTest unravels LINE-1 retrotransposition in Head and Neck Squamous Cell Carcinoma

Abstract

The relevant role of LINE-1 (L1) retrotransposition in cancer has been recurrently demonstrated in recent years. However, their repetitive nature hampers their identification and detection, hence remaining inaccessible for clinical practice. Also, its clinical relevance for cancer patients is still limited. Here, we develop a new method to quantify L1 activation, called RetroTest, based on targeted sequencing and a sophisticated bioinformatic pipeline, allowing its application in tumor biopsies. First, we performed the benchmarking of the method and confirmed its high specificity and reliability. Then, we unravel the L1 activation in HNSCC according to a more extensive cohort including all the HNSCC tumor stages. Our results confirm that RetroTest is remarkably efficient for L1 detection in tumor biopsies, reaching a high sensitivity and specificity. In addition, L1 retrotransposition estimation reveals a surprisingly early activation in HNSCC progression, contrary to its classical association with advanced tumor stages. This early activation together with the genomic mutational profiling of normal adjacent tissues supports field cancerization process in this tumor. These results underline the importance of estimating L1 retrotransposition in clinical practice towards an earlier and more efficient diagnosis in HNSCC.