DNA manipulation

Chaos in cancer cells: Mysterious gene transcripts after therapy

Drugs that are used in cancer therapy to erase epigenetic alterations in cancer cells simultaneously promote the production of countless mysterious gene transcripts, scientists from the German Cancer Research Center (DKFZ) now report in Nature Genetics. The substances activate hidden regulatory elements in DNA. The unusual gene activity has the potential to stimulate the immune system – a previously unnoticed effect that may increase the effect of therapeutic agents.

Photo: Chaos in cancer cells: Mysterious gene transcripts after therapy
Source: Schuster/DKFZ

Tumor suppressor genes protect cells from malignant transformation. If they are turned off as a result of chemical modifications in DNA, called epigenetic labels, this contributes to the development of cancer. As opposed to gene mutations, these epigenetic changes are reversible and it is possible to use specific drugs to erase them. “This has been successfully done for years now in various cancers such as acute myeloid leukemia and myelodysplastic syndrome,” said Christoph Plass from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg. He added that it has also been proven that dangerous labels such as on tumor suppressor genes can be removed in this way. “However, the agents pass over the DNA like a lawn mower and remove practically all labels,” said Plass, who also serves as a research coordinator within the German Cancer Consortium (DKTK). “And so far nobody has studied in detail what effect this has on the tumor cells.”

Plass and his co-workers have now pursued this question in collaboration with colleagues from the U.S.A. Using genome-wide analyses, the scientists discovered that countless mysterious gene transcripts arise in the wake of treatment. This is due to an activation of specific regulatory elements in DNA, called promoters, which have been largely unnoticed so far. “There is total chaos in the treated cancer cells – we hadn’t expected that,” said David Brocks, who is one of the first authors of the study. A closer look has shown that the activated regulatory elements originate from viruses that inserted themselves into the genome in the ancient past. However, they were turned off in the course of evolution, thus becoming normal components of DNA.

Protein fragments that form on the basis of these peculiar gene transcripts have the potential to be recognized by the immune system and, thus, to stimulate the immune system. This might increase the effectiveness of drugs that are being used. “Now we have to investigate whether this effect can be used specifically to improve therapy,” Plass said. And yet another aspect: ”These gene transcripts might be useful as biomarkers to examine whether an epigenetic therapy is effective and reasonable in the individual patient.”

 

Source: The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

12.06.2017

Read all latest stories

Related articles

Structural insights

Cancer cells may streamline their genomes to proliferate more easily

Research from the Stowers Institute provides evidence suggesting that cancer cells might streamline their genomes in order to proliferate more easily. The study, conducted in both human and mouse…

It's all connected

Understanding the "wiring diagrams" of genes in complex tissues

How is the activity of all genes in cells of higher organisms interconnected? And how are the genetic "wiring diagrams" of the cells in complex tissues coordinated with each other?…

Brain cancer

Typical mutation in cancer cells stifles immune response

The exchange of a single amino acid building block in a metabolic enzyme can lead to cancer. In addition, it can impair the immune system. It thus blocks the body’s immune response in the battle…

Related products

Research use only (RUO)

Eppendorf - Mastercycler nexus X2

Eppendorf AG

Amplification/Detection

Agena Bioscience - MassARRAY Colon Panel

Agena Bioscience GmbH

Research use only (RUO)

Eppendorf - BioSpectrometer fluroescence

Eppendorf AG

Research use only (RUO)

Eppendorf - μCuvette G1.0

Eppendorf AG

Amplification

Orion Diagnostica Oy - Orion GenRead

Orion Diagnostics Oy