What is Sarcoma? A new study may have identified its origins | NFCR


Sarcoma Origin Identified

sarcoma cancer ribbon
Cancer is anything but a straightforward disease; one tumor type can be entirely different from another not only in location, but causal agent and origin. There is differentiation even within the same type of cancer. Take sarcoma, which is in fact an umbrella term for nearly 100 cancers originating in the skeleton or the soft parts of the body. Some affect the young, others the elderly. But now a study out of Sweden is bringing the starting points of some sarcomas into focus by identifying for the first time an interaction between specific proteins.

“We now know which mechanisms to shine the spotlight on,” says Pierre Åman, Professor of Tumor Biology at Sahlgrenska Academy, University of Gothenburg, the corresponding author behind an article published in the journal EMBO Reports.

Osteosarcomas develop in bone; liposarcomas form in fat; rhabdomyosarcomas form in muscle; Ewing sarcomas form in bone and soft tissue, and Kaposi’s sarcoma is practically synonymous with HIV/AIDS infection. However, among cancers, sarcoma is relatively uncommon; in the United States, around 12,750 people — 7,240 men and boys and 5,510 women and girls  — will be diagnosed with a soft-tissue sarcoma (STS) this year. The overall five-year survival rate for people with STS is around 65 percent; if the cancer is caught early and has not left its point of origin, the survival rate can be as high as 81 percent; if the sarcoma has spread to another area of the body, the 5-year survival rate falls precipitously to 16 percent. However, rates vary based on the specific type and the stage, or extent, of the sarcoma, showing how even just one type of cancer can have wildly different subsets.

In the Swedish study, the 15 or more different forms of sarcoma studied were found to be caused by mutations in the FET family of proteins, involved in the regulation of lifespan and stress resistance, acting partially through the insulin/IGF-signaling pathway. The new results show that most of the tumor-altered FET proteins bind to another protein complex, SWI/SNF, which regulates gene activity, cell maturity and growth. This interaction results in SWI/SNF misregulation and, accordingly, disruptions in the genetic programming within a cell. The misregulation is a mechanism common to all the 15 or more forms of tumor caused by mutations in the FET genes. This now gives oncologists a solid target upon which to aim their efforts, and could clear the way for some type of screening technology.

Importantly, the FET family is already a focus of scientific inquiry: they are of medical interest because chromosomal rearrangements of their genes promote not only various sarcomas, but because point mutations in FUS or TAF15 (both FET) can cause neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar dementia.

Because of that, “There are already an abundance of new drug candidates that affect this protein complex and are being tested on other diseases,” Åman says. “With the discoveries we’ve now made, we can test the same candidates on these forms of sarcoma as well.”

July is Sarcoma Awareness Month, and studies such as Åman’s continue to shed light on the cancer’s ultimate cause. Although easy to cure in its early stages, the symptoms of STS are fairly innocuous: a lump or swelling; pain only occurs if the tumor happens to press on a nerve. But if the lump persists, grows, or is located deep within the muscle, people are urged to see their doctor.

American Association for Cancer Research. (2019). Shedding Light on Sarcoma. Retrieved from: https://www.aacrfoundation.org/Pages/sarcoma_awareness_month.aspx
Cancer.net. (2019). Sarcomas of Specific Organs: Statistics. Retrieved from: https://www.cancer.net/cancer-types/sarcomas-specific-organs/statistics
Kubista, Margareta. (2019). Breakthrough in knowledge of how some sarcomas arise. Retrieved from: https://sahlgrenska.gu.se/english/research/news-events/news-article//breakthrough-in-knowledge-of-how-some-sarcomas-arise.cid1624482
Schwartz, Jacob C. (2015). Biochemical Properties and Biological Functions of FET Proteins. Retrieved from: https://www.annualreviews.org/doi/10.1146/annurev-biochem-060614-034325
Therrien, Martine, et al. (2016). FET proteins regulate lifespan and neuronal integrity. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846834/