A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcomas can arise in any of these types of tissues. As a result, there are many subtypes of sarcoma, which are classified based on the specific tissue and type of cell from which the tumor originates. Sarcomas are primary connective tissue tumors, meaning that they arise in connective tissues. This is in contrast to secondary (or "metastatic") connective tissue tumors, which occur when a cancer from elsewhere in the body (such as the lungs, breast tissue or prostate) spreads to the connective tissue. The word sarcoma is derived from the Greek σάρκωμα sarkōma "fleshy excrescence or substance", itself from σάρξ sarx meaning "flesh".

The cause of most bone sarcomas is not known, but several factors are associated with an increased risk of developing bone sarcoma. Previous exposure to ionizing radiation (such as prior radiation therapy) is one such risk factor.Exposure to alkylating agents, such as those found in certain cancer chemotherapeutic medicines, also increases the risk of bone sarcoma.Certain inherited genetic syndromes, including Li-Fraumeni syndrome, heritable RB1 gene mutations, and Paget's disease of bone, are associated with an increased risk of developing bone sarcomas.

Most soft tissue sarcomas arise from what doctors call "sporadic" (or random) genetic mutations within an affected person's cells. Nevertheless, there are certain risk factors associated with an increased risk of developing soft tissue sarcoma. Previous exposure to ionizing radiation is one such risk factor. Exposure to vinyl chloride (e.g., such as the fumes encountered in the production of polyethylene vinyl chloride (PVC)), arsenic and thorotrast all are associated with an increased risk of angiosarcoma. Lymphedema, such as that resulting from certain types of breast cancer treatment, also is a risk factor for development of angiosarcoma.As with bone sarcomas, certain inherited genetic syndromes also are associated with an increased risk of developing soft tissue sarcoma, including Li-Fraumeni syndrome, familial adenomatous polyposis, neurofibromatosis type 1, and heritable RB1 gene mutations.

The mechanisms by which healthy cells transform into cancer cells are described in detail elsewhere (see Cancer main page; Carcinogenesis main page). The precise molecular changes that result in sarcoma are not always known, but certain types of sarcomas are associated with particular genetic mutations. Examples include:

Most cases of Ewing sarcoma are associated with a chromosomal translocation in which part of chromosome 11 fuses with part of chromosome 22. This results in the EWS gene becoming fused to other genes, including the FLI1 gene in 90% of Ewing cases and ERG gene in 5-10% of cases. These fusions result in the production of abnormal proteins, although how these abnormal proteins result in cancer is not fully known.

Dermatofibrosarcoma protuberans often is associated with a chromosomal translocation in which the COL1A1 gene becomes fused to the PDGFRB gene. This results in over-active PDGF signaling, which is thought to promote cell division and ultimately lead to tumor development.

Inflammatory myofibroblastic tumor often is associated with rearrangements of the ALK gene, and occasionally with rearrangements of the HMGA2 gene.

Giant cell tumor of soft tissue frequently is associated with a chromosomal translocation between chromosome 1 and chromosome 2, in which the CSF1 gene becomes fused with the COL6A3 gene. This results in increased CSF1 protein production, which is thought to play a role in cancer development.

Many liposarcomas are associated with duplication of part of chromosome 12, which results in extra copies of known cancer-promoting genes ("oncogenes") such as the CDK4 gene, the MDM2 gene and the HMGA2 gene.

Regards
Amalia
Managing Editor
Journal of Clinical Oncology and Cancer Research