Exploring the functional impact of transposable elements in human cancer genomes

Abstract

Approximately half of our genome is composed by genomic sequences with the ability to move from one place to another, being integrated into a new location. These sequences are known as mobile or transposable elements. Among them, retrotransposons can copy and insert themselves into a new region, in a process known as retrotransposition. In the context of cancer, somatic retrotransposition may have important consequences for the evolution of a tumour. LINE-1 -L1- is the only autonomous type of retrotransposon that remains active in the human genome, being highly active in cancer, specifically in certain tumour types such as oesophagus, head and neck, lung and colorectal tumours. This PhD thesis aimed to explore the structural and functional impact of somatic retrotransposon insertions, particularly L1 retrotransposition, in the context of human cancers. In the first part of this work, we have developed the “RetroTest”, a new method to measure somatic L1 activity in tumours. This tool can be applied to a broad variety of sample sources, working even in FFPE tumour biopsies, which makes it an attractive method to be applied in clinics.