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New Possibilities Tumor Research

New Possibilities Tumor Research

New Possibilities Tumor Research

New Possibilities Tumor Research

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Blood tests are becoming an important tool in the diagnosis and monitoring the course of therapy of cancer patients. Are particularly promising new approaches that are based on the analysis of small fragments of the genome of tumor cells, which will be issued from these in the bloodstream. The genetic material of tumor cells differs from the known by normal cells through changes, mutations, which can affect the functional units called genes, so that they make their task proteins (proteins), no longer or only partially run.So far, the analysis from the blood allowed to draw just conclusions on mutations in the tumor genome, but not how this has also the function of individual genes is altered. Scientists at the Medical University of Graz and the Graz University of Technology, it is now managed to predict by a blood test, the gene expression of individual genes in the tumor tissue of breast cancer patients, which could be significantly expanded the diagnostic possibilities and eventually enable treatment decisions for cancer patients. 

ctDNA: Tiny fragments of the tumor genome under the scientists'  

The analysis of fragments of the tumor genome in the blood, also known as circulating tumor DNA (Engl .: circulating tumor DNA; ctDNA) referred, currently rapidly developed into an important tool in the diagnosis and monitoring of cancer patients. "The cost method is a very good alternative to expensive and sometimes invasive examination methods in cancer diagnosis and therapy in the control," explains Peter Ulz , Institute of Human Genetics at the Medical University of Graz and author of the study. The background of the method is that dying tumor cells secrete tiny genetic fragments in the blood, from which can be read off tumor-specific mutations. "It provides the blood test to draw conclusions about the genetic makeup of the tumor and its development during therapy," said Peter Ulz. However, the detection of ctDNA has its limits, as currently only static changes at the DNA level can be read, such as point mutations or copy number changes. Important dynamic markers, such as the expression of individual genes, however, could not be analyzed until now.

Discovery: First conclusions about gene expression in tumor tissues detected  

This fact employed an interdisciplinary team under the inter-university research collaboration BioTechMed-Graz around the Institute of Human Genetics at the Medical University of Graz and the Institute of Molecular Biotechnology of the Technical University of Graz.

Starting point is the process of transcription, the first step in gene expression, ie the process by which the genetic information is expressed or the genotype expresses - as healthy tissue or tumor tissue. The circulating in the blood DNA is derived primarily from cells that have undergone apoptosis. The DNA is cleaved by enzymes and there is a typical fragment pattern. Since certain proteins are attached at defined intervals to the DNA (nucleosomes), areas which are linked to proteins, not degraded. "A certain control range control region of active genes, however, is not protected by such proteins from degradation and thus cleaving DNA enzymes preferably digested," Peter Ulz describes the process. The transcription of genes thus always leaves a trace on the DNA in the peripheral blood. "By sequencing of all fragments in the peripheral blood, can now be concluded due to the lack of individual fragments on gene expression," said Peter Ulz.

In a first step, the scientists have shown that circulating in the blood DNA fragments are in fact associated with nucleosomes and thus are increasingly being used for sequencing are available. In a further step, it is the researchers succeeded prove that the fragment pattern differs in healthy test subjects between active and non-active genes. Supported by machine learning could the scientists about the absence of these fragments predict which gene is actively expressed, and which does not, the prediction agrees well with experimental values.

Dynamic markers in cancer therapy  

The technology developed by the researchers analysis was used to study blood samples from breast cancer patients to predict gene expression of individual genes in regions of copy number increases. "To The comparison with experimental data from the gene expression analysis of primary tumor tissue of the patients we were able to show that our analysis is capable of expressing non-expressed genes differ," Peter Ulz summarizes. Thereby, it might be possible also in other types of cancer in the future, in addition to the static information of the tumor genome, functional information, such as gene expression, derived from analysis of ctDNA. This could help to better and more comprehensive to track changes in the tumor genome that arise in the course of cancer in order to get a greater insight into tumor biology. What consequences could have the information gained on the treatment strategies for different cancers, can be even more difficult to estimate, the hope would, however, be able to respond to a change in the tumor quickly and with appropriate, targeted therapies. In the long run this approach could thus pursue personalized medicine further and provide the benefits of ctDNA analyzes further to the fore.