Final Report Summary - CANCER INSERTOME (THE LANDSCAPE AND FUNCTIONAL IMPACT OF TUMOUR-SPECIFIC GENOMIC INSERTIONS OF 1,000 CANCER GENOMES) Retrotransposition of transposable elements is quite common in cancer. We analyzed the whole-genome sequencing data of several hundreds of tumour/normal genome pairs. We found that about half of cancer genomes have at least one retrotransposition event, with lung and colorectal cancers most frequently affected (93% and 75% of patients, respectively). We have rediscovered a new mutational process in cancer genomes called L1-mediated 3' transduction. Somatic 3’-transductions comprised 24% of all somatic retrotranspositions. Overall, 95% of 3’-transductions identified derived from only 72 germline L1 source elements, with as few as four loci accounting for 50% of events. About 5% of somatic transductions arose from L1 source elements that were themselves somatic retrotranspositions. The activity of individual source elements fluctuated during tumour evolution, with different subclones exhibiting much variability in which elements were ‘on’ and which were ‘off’. 3’-transduction activity in a patient’s tumour was always associated with hypomethylation of that element. Overall, 2.3% of transductions distributed exons or entire genes to other sites in the genome, and many more mobilized regulatory regions.We concluded that retrotransposition in cancer represents an important new level of variation that has to be analyzed from now on in every single sequenced cancer genome. The identification if this structural variation will lead to the identification of new mutated genes, and will be important for therapy purposes.Web link to the summary of main results: http://www.sanger.ac.uk/about/press/2014/140807-line1.html
