Uncommon cancer gets start in muscle cells

A cancer thought to arise in joint tissue instead forms in nascent muscle cells, a study in mice shows. By creating for the first time an animal that develops this cancer, known as synovial sarcoma, the researchers clear the way for similar research into other sarcomas and for possible drug development.

Synovial sarcoma is so named because it arises near the synovium, the membrane that makes the lubricant for joints. Not all cancers readily reveal their cells of origin, however, and previous studies hadn’t established that the cells of this cancer begin as synovial cells.

Meanwhile, that research found that synovial sarcoma cells have a characteristic DNA arrangement. In these cells, two genes from separate chromosomes fuse and encode a rogue protein called SYT-SSX that scientists suspect influences cell growth.

Researchers developed mice that make the aberrant protein in muscle cells during various developmental stages. All mice that made the protein in early-stage muscle cells developed synovial sarcoma tumors, says geneticist Mario R. Capecchi of the Howard Hughes Medical Institute and the University of Utah School of Medicine in Salt Lake City. He and his colleagues report the findings in the April Cancer Cell.

The fusion protein failed to induce malignant growth during other stages of muscle-cell maturation or in other cell types.

Fusion proteins are a common and random occurrence in the body, and they often show up in sarcomas, Capecchi says.

The new study has importance for sarcoma research in general because it shows the “remarkable specificity” required for such aberrant proteins to initiate a cancer and suggests that only specific cell types are susceptible to their transforming effects, say Sean R. Davis and Paul S. Meltzer of the National Cancer Institute in Bethesda, Md., writing in the same journal issue.