A recent study uncovers several newly identified genetic mechanisms associated with aggressive forms of Ewing sarcoma, including previously unrecognized genes. These mechanisms drive metastasis and contribute to poorer prognoses. By integrating gene expression data from patients and cellular models, researchers pinpointed a gene signature linked to worse outcomes. This discovery broadens the scope of potential prognostic markers and therapeutic targets, offering insights into managing the most severe cases of Ewing sarcoma.
The research, published in EMBO Reports, was spearheaded by Dr. Ana Losada, head of the Chromosomal Dynamics Group at Spain’s National Cancer Research Centre (CNIO).
Ewing sarcoma is a rare but aggressive tumor affecting bones and soft tissues, primarily in children and young adults. It occurs in approximately 9 to 10 cases per million people annually. Despite treatment advances, about 25% of patients do not respond well to standard therapies and often experience relapses, underscoring the need for improved therapeutic strategies.
Losada explained to Inside Precision Medicine that the most common treatment approach involves a combination of systemic chemotherapy, surgery, and/or radiation therapy to control the local tumor. The current chemotherapy regimen typically includes vincristine, doxorubicin, and cyclophosphamide (VDC), alternated with ifosfamide and etoposide (IE), or sometimes VDC/IE.
The recent discovery by Losada and her team opens up new possibilities for treatment options, as it “provides a list of potential biomarkers and therapeutic targets,” according to the authors.
Ewing sarcoma is caused by the abnormal fusion of two genes, creating an oncogene. The protein produced by this oncogene activates the expression of genes that promote tumor growth. While it was previously known that the lack of the STAG2 protein intensifies the oncogene’s harmful effects, this new study reveals that alterations in the expression of many other genes also occur.
Ana Cuadrado, PhD, the study’s corresponding author, explains that the loss of STAG2 “also alters the expression of other genes that are not controlled by the oncogene, and these changes further increase tumor aggressiveness.”
STAG2 is a component of cohesin, a protein complex essential for cellular life, first identified by Losada in the late 1990s. Cohesin plays a critical role in cell division and gene expression processes. It functions as a ring that holds chromosomes together during duplication in cell division.
When the cell is not dividing, cohesin helps bind the DNA, allowing it to fold properly, which is crucial for ensuring that genes are read accurately.
This study, published in EMBO Reports, demonstrates that the absence of STAG2 leads to incorrect DNA folding, disrupting the expression of many genes.
Here you will find the report.
Resource: insideprecisionmedicine.com
Sarcomafree Foundation is a non-profit organization dedicated to providing comprehensive information about sarcoma. We welcome your suggestions for topics or feedback, so please don’t hesitate to reach out and share your thoughts with us!
