“Jumping gene” uncovers genetic networks involved in prostate and breast cancer

Mutations in tumour suppressor genes mean that they can no longer keep tumours from growing. In developing cancer, often several mutations come into play. Using "jumping genes," scientists from the Technical University of Munich (TUM) and the German Cancer Consortium (DKTK) together with teams from Great Britain and Spain have identified a number of genes that can influence the growth of prostate and breast tumours.
Prostate cancer is the most common cancer in men in Germany with around 63,000 patients diagnosed every year. About half of them have an altered Pten gene. This well-known tumour suppressor gene can help prevent cancer development in healthy people by inducing cell death in tumour cells. However, little is known about which other genes cooperate with Pten to prevent cancer. In order to find out more, the international team designed a new method. They converted the Pten-Gene in mice into a mobile DNA element known as a transposon. This transposon "jumps" from its original position and lands at a random position throughout the genome, damaging and thus deactivating genes into which it is inserted. The transposons "starting point", i.e. the Pten-Gene, is deactivated as well. In the experiment, cancers would grow when the transposon damaged a tumour suppressor gene that co-operated with Pten.
"Using the new transposon-based approach, we were able to systematically search the genome for genes cooperating with Pten and influencing the development of prostate cancer, but also other forms of cancer like breast or brain cancer," says Dr Juan Cadiñanos, joint lead author from the Instituto de Medicina Oncologica y Molecular de Asturias and the Wellcome Trust Sanger Institute in Britain. "This approach could also be used to look into relations between other genes."
The researchers analysed 278 prostate, breast and skin tumours and revealed hundreds of genes that could cooperate with Pten and act as further tumour suppressor genes. Human cell lines and data from human prostate tumours were then used to study the five most promising genes. "Coupled with Pten inactivation, a loss of function in these genes led to typical cancer pathways being activated," says Jorge de la Rosa, one of the study’s first authors. The researchers found that in human prostate tumours, the genes in question were considerably limited in their function.
Transposon-based approaches are useful for looking into the molecular basics of the development of tumours. "They allow us to find genes connected to cancer that are hard to find using other methods," says Roland Rad, a DKTK-Professor for translational Oncology at TUM’s Klinikum rechts der Isar. "In order to understand the biology of tumour development, we must uncover the complex tumor suppressor networks. This is a prerequisite for developing new therapeutic strategies."

DKFZ
www.dkfz.de/en/presse/pressemitteilungen/2017/dkfz-pm-17-14b-Jumping-gene-uncovers-genetic-networks-involved-in-prostate-and-breast-cancer.php