Hereditary sarcoma

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Ewing sarcoma is a malignant growth that can manifest in either bones or soft tissues, such as nerves or cartilage. There are various forms of Ewing sarcoma, including bone Ewing sarcoma, extraosseous Ewing sarcoma, peripheral primitive neuroectodermal tumor (pPNET), and Askin tumor. These tumors share a common genetic origin and can be differentiated based on the tissue in which they develop. The majority of Ewing sarcomas, around 87%, are bone Ewing sarcomas, which typically occur in the femurs, pelvis, ribs, or shoulder blades.

Ewing sarcoma is commonly caused by a mutation involving two genes: the EWSR1 gene located on chromosome 22 and the FLI1 gene located on chromosome 11. This mutation occurs through a translocation of genetic material between the two chromosomes, denoted as t(11;22), which results in the fusion of a portion of the EWSR1 gene with a portion of the FLI1 gene, forming the EWSR1/FLI1 fusion gene. This mutation is acquired during an individual's lifetime and is only present in tumor cells, making it a somatic mutation that is not inherited.

The EWSR1/FLI1 fusion gene produces a protein known as EWS/FLI, which combines the functions of both genes. FLI1's protein product binds to DNA and regulates transcription, the initial step in protein production from genes. By controlling the transcription of specific genes, FLI1 regulates the growth and development of certain cell types. Similarly, EWSR1's protein product also regulates transcription. EWS/FLI possesses both the DNA-binding function of FLI1 and the transcription regulation function of EWSR1. It is believed that EWS/FLI abnormally turns on and off the transcription of various genes, leading to uncontrolled proliferation, abnormal maturation, and survival of cells, ultimately resulting in tumor development.

Around 85% of Ewing sarcomas exhibit the EWSR1/FLI1 fusion gene. Although rare, other gene translocations that merge the EWSR1 gene with genes linked to FLI1 can also lead to these tumors. Despite their infrequency, the fusion proteins resulting from these alternative gene translocations perform the same role as the EWS/FLI protein.

Follow the link of the selected polymorphism to read a brief description of how the selected polymorphism affects Sarcoma and see a list of existing studies.

SNP polymorphisms related to the topic Sarcoma: