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Epigenetic analysis: Giving the right name to a tumor

March 15, 2018

The "Hopp Children's Cancer Center at the NCT Heidelberg" (KiTZ) is a joint institution of Heidelberg University Hospital (UKHD) and the German Cancer Research Center (DKFZ).

To be able to treat cancer of the central nervous system (CNS) successfully, it is important to have very precise knowledge about the molecular characteristics of the tumors in order to "give them the right name". It is presently possible to differentiate about 100 types of CNS tumors based on tissue characteristics. These tumor types show widely varying responses to radiotherapy and chemotherapy. In some cases, methods of molecular diagnostics are used to further classify tumors, for example based on certain gene mutations. Nevertheless, their variability is large, which makes it difficult to standardize diagnostic methods.

In order to enhance the diagnosis of CNS tumors, a team led by Professor Stefan Pfister, KiTZ director and department head of "Pediatric Neurooncology" at the DKFZ, in collaboration with colleagues from the Neuropathology Department at Heidelberg University Hospital led by Professor Andreas von Deimling, have developed a new computer-based method. "We hope that our new molecular classification method will help improve diagnostic accuracy in CNS tumors and, thus, also improve the chances for successful treatment," said von Deimling.

The researchers analyzed specific chemical tags in the tumor genomes called DNA methylations. Different cell types exhibit characteristic patterns of DNA methylation which enable scientists to draw conclusions about a tumor's cellular origin. "We have developed computer-based algorithms that reliably differentiate 82 types of CNS tumors based on their methylation patterns," said Professor David Capper, who is one of the four first authors of the study. Capper is a faculty member of the DKTK partner site in Berlin and has recently accepted a professorship for Molecular Neuropathology at Charité University Medicine Berlin. "Particularly in tumors which we cannot easily assign to a diagnostic category based solely on microscopic examination, methylation analysis is often helpful to make a precise diagnosis. The analysis of approximately 2,800 reference tumor samples additionally made it possible to classify tumors into specific subgroups that are not yet included in the classifications that have been used so far."

Use in the clinic

In order to test whether the method is suitable for use in clinical routine diagnostics, the scientists analyzed more than 1,100 additional tumor samples. In about twelve percent of the cases, they were able to correct the initial diagnosis using the methylation patterns. In almost all cases where it was possible, further molecular-diagnostic examinations showed that molecular classification characterized the tumors even better than the initial microscopic diagnosis.

"We are convinced that our new method is well suited to be used in the clinic," said Pfister. He added: "We have made our classification system available online in order to enable researchers to analyze their data at our platform." The information that will come in this way will at the same time help achieve more precise diagnoses and, thus, better treatment of rarer cancer types.
-end-
The online platform on DNA methylation analysis is available at: http://www.molecularneuropathology.org.

Deutsche Kinderkrebsstiftung provided substantial support for the project.

Original publication: Capper D., Jones D.T.W. Sill M. and Hovestadt V. (joint first authorship) et al. (2018) "DNA methylation-based classification of central nervous system tumours". Online publication March 14th 2018; doi:10.1038/nature26000

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

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.

Heidelberg University Hospital and Medical Faculty: Internationally recognized patient care, research, and teaching

Heidelberg University Hospital is one of the largest and most prestigious medical centers in Germany. The Medical Faculty of Heidelberg University belongs to the internationally most renowned biomedical research institutions in Europe. Both institutions have the common goal of developing new therapies and implementing them rapidly for patients. With about 13,000 employees, training and qualification is an important issue. Every year, around 65,000 patients are treated on an inpatient basis, 56,000 cases on a day patient basis and more than 1,000,000 cases on an outpatient basis in more than 50 clinics and departments with almost 2,000 beds. Jointly with the German Cancer Research Center (DKFZ) and German Cancer Aid, Heidelberg University Hospital has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. Currently, about 3,700 future physicians are studying in Heidelberg; the reform Heidelberg Curriculum Medicinale (HeiCuMed) is one of the top medical training programs in Germany. http://www.klinikum.uni-heidelberg.de

The "Hopp Children's Cancer Center at the NCT Heidelberg" (KiTZ)

The "Hopp Children's Cancer Center at the NCT Heidelberg" (KiTZ) is a joint institution of the Heidelberg University Hospital and the German Cancer Research Center (DKFZ). As a therapy and research center for oncologic and hematologic diseases in children and adolescents, the KiTZ is committed to scientifically exploring the biology of childhood cancer and to closely linking promising research approaches with patient care- from diagnosis to treatment and aftercare. Children suffering from cancer, especially those with no established therapy options, are given an individual therapy plan in the KiTZ, which is created by interdisciplinary expert groups in so-called tumor boards. Many young patients can participate in clinical trials which ensures access to new therapy options. Thus, the KiTZ is a pioneering institution for transferring research knowledge from the laboratory to the clinic.

Heidelberg University Hospital and Medical Faculty

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