A group of researchers led by the head of Chromosome Dynamics Group of the National Cancer Research Center (CNIO), Ana Losada, have identified several mechanisms that increase the aggressiveness of Ewing’s sarcoma.
It is a very aggressive tumor of bones and soft tissues that occurs in children and young people, which opens new avenues for the search for treatments, since a 25 percent of patients do not respond well to usual treatment and frequently present recurrences.
“(The survey) provides a list of potential biomarkers (prognosis) and therapeutic targets”, explained the scientists, who recognized mechanisms that promote metastases and give rise to a more serious course of the disease, which is rare (nine cases per million inhabitants per year), according to a press release from the CNIO.
Ewing’s sarcoma is caused by the abnormal fusion of two genes, which gives rise to an oncogene, which in turn produces a protein that causes the expression of genes favoring the development of the tumor and, although it was known already that the lack of protein ‘STAG2’ amplifies the “pernicious effect” of the oncogene, Cuadrado pointed out that its absence “also modifies the expression of other genes that do not depend on the oncogene, and these changes also increase the aggressiveness of the tumor.”
The aforementioned protein “is part of a protein complex essential for life, cohesin”, which is key for cell division and the process of reading or expressing genes, help DNA fold and acquires the appropriate spatial conformation, important so that gene information can be read correctly.
The study, funded by the Spanish Association Against Cancer (AECC) and the National Research Agency (AEI), and published in “EMBO Reports”, showed that the absence of “STAG2” causes “incorrect” folding of DNA, leading to failures in the expression of many Genoa.
“The cohesion which carries STAG2 moves along DNA form links that facilitate physical contact between the elements that control the reading of many genes; if it disappears, gene expression becomes more difficult. The cells survive, but with many aberrations that make them more aggressive,” Losada explained.
Likewise, he said that identifying more genes affected by the lack of this cohesin is what “opens the door to studying how each of them contributes to the aggressiveness of tumors,” after which he gave the example of future studies that compare genes. immunological response of patients affected and no mutations in ‘STAG2’which could help to understand whether tumors without “STAG2” escape the immune system better, which which would be “very useful” when applying immunotherapy for Ewing sarcoma.
The scientist also said that the loss of this protein could affect the stability of the genome itself, affecting various mechanisms that worsen the prognosis, Therefore, “it is necessary to elucidate each of these mechanisms, in order to provide new treatment options for patients with mutations affecting cohesin.”
