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NCT/DKTK-MASTER: Cancer genome analysis nearing clinical application

Press Release of the NCT Heidelberg

Scientists today are able to observe tumor cells in increasing detail and thus gain a better understanding of how cancer cells differ from healthy ones. Doctors and scientists from the National Center for Tumor Diseases (NCT), the Institute of Pathology at Heidelberg University Hospital (UKHD) and the German Cancer Consortium (DKTK) completed a prospective study that systematically verified data on cancer genome analysis. Conducted over a period of three years, the study examined more than 200 patients with tumor diseases that are at an advanced stage or difficult to treat who underwent a cancer genome analysis within the scope of the NCT/DKTK-MASTER program. In the validation study as part of the program, the scientists show how comprehensive cancer genome analysis and evaluation can be optimized in such a way that they can be used for clinical application.

 The National Center for Tumor Diseases (NCT) Heidelberg is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital (UKHD), and German Cancer Aid.

© NCT Heidelberg

In most cancer diseases, the uncontrolled growth of cells is caused by defects in the genetic material. The pattern of genetic changes may differ from patient to patient or even within a tumor. It is therefore important to understand these patterns in order to gain a better understanding of each individual disease. In addition, certain gene mutations are often the point of attack for targeted therapies. Discovering even the smallest genetic defects within a cell requires precise testing methods that examine both the genetic material for defects as well as the protein molecules in a cell. These precise analysis methods include omics technologies, which are new procedures used to create molecular profiles of cells, tissues, and tumors within a short period of time. The technologies for the cancer genome sequencing play a special role, as they can record genetic changes both comprehensively and in detail.

With the MASTER program (Molecularly Aided Stratification for Tumor Eradication), the NCT Heidelberg along with its partners based in Heidelberg, DKFZ, and UKHD, has created the infrastructures required to make comprehensive cancer genome analysis an integral part of molecular diagnosis in clinical practice. The program has been extended to all seven DKTK partner sites in Germany, also by setting up and networking among the molecular tumor boards. NCT and UKHD offer cancer patients wide-ranging molecular analysis tailored to match the individual clinical situation. Complementary to the specific genome analysis which is available to all oncology patients at the Heidelberg sites who have been given the corresponding clinical diagnosis, the MASTER program strives to identify new tumor treatment approaches adapted to the individual tumor profile for young patients with cancer in advanced stages and patients with rare forms of cancer by applying a wide-ranging cancer genome analysis.

In the present study, researchers analyzed more than 200 cancer patients at all DKTK sites during the period from 2013 to 2016 who underwent comprehensive cancer genome analysis within the scope of the MASTER program. The tests aimed to verify the discovered gene changes by using established methods long since used in cancer diagnosis.

The detailed analyses and control steps enabled the researchers to improve the work procedures and processes for the molecular analysis of cancer patients and increase the reliability of the resulting clinical statements. “We can now say with more certainty that the analysis in the MASTER program are very reliable; at the same time, we also identified and eliminated weaknesses. This applies, in particular, to detecting so-called gene fusions, which often occur in cancer. The results are an important step on the path towards the wide clinical application of molecular analysis,” says Professor Stefan Fröhling, Managing Director of the NCT Heidelberg.

“The MASTER validation study is currently the world’s largest and most systematic of its kind. In North America, there are very few programs that take a similar approach,” comments Professor Albrecht Stenzinger, Director of the Molecular Pathology Center at UKHD. “The comprehensive study would not have been possible without the exemplary interdisciplinary collaboration of doctors, molecular biologists, bioinformaticians, geneticists and pathologists and the cooperation between the various institutions.”

Since 2016, additional patients have undergone molecular analysis in the MASTER program. “We have evaluated the tumor genomes of more than 1,100 patients and adapted the planned therapies based on these results,” Fröhling added.

Point of contact for patients and referring physicians
To register or ask questions about the NCT MASTER program, please send an email to the study office at master@nct-heidelberg.de. Currently, young patients (< 50 years of age) or patients with rare tumors are included in the study.

Original publication:
A. Lier, R. Penzel, C. Heining et al. (2018) Validating Comprehensive Next-Generation Sequencing Results for Precision Oncology: The NCT/DKTK MASTER Experience. JCO Precision Oncology. DOI 10.1200/PO.18.00171