Press and Public Relations

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

No. 14b | 21/03/2017 | by AM

Mutations in tumor suppressor genes mean that they can no longer keep tumors 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 tumors. They published their results in "Nature Genetics".

Prostate cancer cells under the microscope.
© Lukasz Kacprzyk / DKFZ

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 tumor suppressor gene can help prevent cancer development in healthy people by inducing cell death in tumor 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 tumor 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 tumors and revealed hundreds of genes that could cooperate with Pten and act as further tumor suppressor genes. Human cell lines and data from human prostate tumors 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 tumors, 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 tumors. "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 tumor development, we must uncover the complex tumor suppressor networks. This is a prerequisite for developing new therapeutic strategies."

Original publication:
de la Rosa et. al.*: A single-copy Sleeping Beauty transposon mutagenesis screen identifies new PTEN-cooperating tumor suppressor genes. In: Nature Genetics (20. März 2017) doi:10.1038/ng.3817

* The two first and four last authors have contributed equally to this publication.

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

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