Subset of Ewing Sarcomas Arise from Early, Complex Genome Rearrangements

NEW YORK (GenomeWeb) – A subset of particularly aggressive Ewing sarcomas seem to stem from a complex rearrangement known as chromoplexy that occurs early in cancer development, long before tumors appear, new research suggests.

As they reported online today in Science, investigators from the Hospital for Sick Children (SickKids), the University of Toronto, the Wellcome Trust Sanger Institute, and elsewhere used exome sequencing, whole-genome sequencing, or RNA sequencing to explore the molecular events leading to characteristic EWSR1-ETS gene fusions in Ewing sarcoma, a form of bone and soft tissue cancer typically diagnosed in adolescents or young adults.

Across tumor samples from 124 individuals with Ewing sarcoma, the team uncovered 52 that showed telltale “loop-like” rearrangements stemming from chromoplexy. The analyses suggested these rearrangements lead to fusions such as EWSR1-ETS, while disrupting several other genes — perhaps explaining the apparent ties between chromoplexy and Ewing sarcoma aggressiveness that the group detected.

“We found dramatic early chromosomal shattering in 42 percent of Ewing sarcomas, not only fusing two critical genes together, but also disrupting a number of important areas,” co-corresponding author Adam Shlien, co-director of the SickKids Cancer Sequencing program and associate director of translational genetics, said in a statement.

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