For the first time, the genome of clear cell sarcoma has been analyzed, a rare cancer that affects adolescents and young people and for which there is still no targeted treatment. The studio was led by an Italian-American team led by Huntsman Cancer Institute Disease Centers, specializing in the study of sarcomas at the University of Utah – with the participation of the Nobel Prize Mario Capecchi – and the results are published in the Journal of Clinical Investigation. “The results we have obtained allow us to better understand the biology of this sarcoma,” he explains Emanuele Panza of the Department of Medical and Surgical Sciences of the University of Bologna, first author of the study: “Furthermore, we were able to develop some innovative models that represent an essential tool for testing new preclinical therapies, and getting to fight this disease”.
That DNA defect that gives rise to sarcoma
The term “sarcoma” encompasses many different forms of cancer. Clear cell sarcomas are a very aggressive type of soft tissue sarcoma that develops in the tendons and can be confused with melanoma due to some morphological and molecular characteristics. One of the well-known mutations of this tumor is one translocation which occurs at the level of two genes, EWSR1 and ATF1. Basically, the fragments of two different chromosomes swap places and recompose: this defect gives rise to “fusion” proteins that are defective and that guide the formation of the sarcoma. Apart from this characteristic, however, until today little was known about the rest of the genome of this neoplasm.
The new study
To investigate the presence of any other important and peculiar mutations, the researchers generated a new model of the tumor, reproducing it in mice. They thus identified characteristic alterations in the copy number of some specific genes (in particular the MITF gene) and chromosomes (7 and 8) and induced in vivo the process of chromosomal translocation EWSR1-ATF1. “Overall, this tumor has a relatively stable genome”, explains Panza: “In addition to the chromosomal translocation that generates the EWSR1-ATF1 fusion oncogene, no other secondary mutations have emerged that are essential to initiate the process of disease formation”. But the study of its genome does not stop there: “It is important to continue to study its characteristics – concludes the researcher – and thus to formulate specific therapies”.
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