CeMM: Epigenetic diversity in childhood cancer

Researchers at the St. Anna Children’s Cancer Research Institute (CCRI) and CeMM observed unexpected variety in the epigenome of Ewing sarcoma, an aggressive childhood cancer. This finding, published in Nature Medicine, supports the importance of epigenetics in pediatric tumors and provides new perspectives for developing personalized therapies.

Tumors of the elderly, such as breast cancer and colon cancer, accumulate thousands of DNA mutations. These genetic defects contribute to cancer-specific properties including uncontrolled growth, invasion in neighboring tissues, and evasion from the immune system. Similar properties are also found in childhood cancers, although those tumors carry much fewer genetic defects, making it difficult to explain their clinical heterogeneity.

This is particularly true for Ewing sarcoma, an aggressive bone cancer in children and adolescents. A team of scientists by Eleni Tomazou from the St. Anna Children’s Cancer Research Institute in Vienna found that the disease’s clinical diversity is reflected by widespread epigenetic heterogeneity. Using novel bioinformatic methods developed by Nathan Sheffield at CeMM, the scientists studied the tumors’ DNA methylation patterns.

Ewing sarcoma showed unique characteristics that differ markedly from others cancers, and the DNA methylation patterns also varied between patients. Moreover, the researchers found that Ewing sarcoma tumors appear to retain part of the characteristic DNA methylation patterns of their cell-of-origin. Thus, the diverse clinical courses observed among Ewing sarcoma patients may be explained by the combination of Ewing sarcoma specific and cell-of-origin specific DNA methylation patterns.

“From these new insights into the biology of Ewing sarcoma we expect new impulses for personalized therapy of this aggressive cancer”, Heinrich Kovar, Scientific Director of St. Anna Children’s Cancer Research Institute, optimistically states. “Our findings also provide an interesting concept for other cancer with low genetic complexity. In the era of precision medicine, understanding the causes and consequences of tumor heterogeneity will be crucial to treat in a targeted way”, Christoph Bock, Principal Investigator at CeMM, adds.

Nathan C Sheffield, Gaelle Pierron, Johanna Klughammer, Paul Datlinger, Andreas Schönegger, Michael Schuster, Johanna Hadler, Didier Surdez, Delphine Guillemot, Eve Lapouble, Paul Freneaux, Jacqueline Champigneulle, Raymonde Bouvier, Diana Walder, Ingeborg M Ambros, Caroline Hutter, Eva Sorz, Ana T Amaral, Enrique de Álava, Katharina Schallmoser, Dirk Strunk, Beate Rinner, Bernadette Liegl-Atzwanger, Berthold Huppertz, Andreas Leithner, Gonzague de Pinieux, Philippe Terrier, Valérie Laurence, Jean Michon, Ruth Ladenstein, Wolfgang Holter, Reinhard Windhager, Uta Dirksen, Peter F Ambros, Olivier Delattre*, Heinrich Kovar*, Christoph Bock*, and Eleni M Tomazou* (*jointly directed this work). DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma. Nature Medicine, 30 January 2017. DOI:10.1038/nm.4273

This work was partly funded by the Austrian National Bank (OeNB), a charitable donation from Kapsch Group (http://kapsch.net/kapschgroup), the Austrian Science Fund (FWF), the Human Frontier Science Program, and the Austrian Academy of Sciences.

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