Epigenetic Variation Defines a Disease Spectrum in Ewing Sarcoma

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 many 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 single genetic defect - the EWS-ETS fusion - is present in all tumors, initiating cancer development and defining Ewing sarcoma as a disease. But the tumors carry very few DNA mutations that could explain the observed differences in the disease course of Ewing sarcoma patients. Tackling this question, a team of scientists from Austria, France, Germany, and Spain led by Dr. Eleni Tomazou from the St. Anna Children's Cancer Research Institute in Vienna, Austria profiled many Ewing tumors. They found that the disease's clinical diversity is reflected by widespread epigenetic heterogeneity. Using novel bioinformatic methods developed by Dr. Nathan Sheffield at CeMM, the team studied the tumors' DNA methylation patterns - one of the most important facets of the human epigenome. 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.
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