PiggyBack Transposons Reveal Genes Newly Associated with Pancreatic Cancer

A technique that can identify causes of cancer invisible to genetic sequencing has uncovered large sets of previously unknown pancreatic cancer genes. It is hoped that this study will boost research into a disease that is still poorly understood and for which five-year survival rates have stood at approximately 5 per cent for the past four decades. The technique works by introducing sections of DNA called PiggyBac transposons into the mouse genome. Transposons jump around within the genome, reinserting themselves at random spots and causing a different mutation in each cell of the mouse. This triggers cancer development, and tracking the transposon´s fingerprints in the tumors allows discovery of the affected cancer-causing genes. The PiggyBac tool was engineered for the first time to allow cancer induction in individual tissues within the mouse, and the method can now be used to study any type of cancer. While genome sequencing can identify all categories of genetic alterations with high accuracy, some of these changes are difficult to interpret. For example, hundreds or thousands of genes are found to be transcriptionally or epigenetically dysregulated within a cancer, meaning that they are not mutated but just being turned on or off. Pinpointing the few cancer-causing events among these large gene sets is extremely difficult. PiggyBac screening can facilitate this search for the needle in the haystack because transposons jump directly into the relevant genes. Moreover, the tool monitors tumor development in mice and, therefore, researchers are also able to see the consequences of cancerous mutations and how they help the disease to progress. "Recent advances in cancer genome sequencing have given extraordinary insights into the genetic events underlying cancer.
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