Integrated modelling and therapeutic applications of bone soft tissue sarcoma by fusion gene expression

Abstract

Sarcomas arise from non-epithelial tissue, such as muscle and cartilage. They represent approximately 1% of cancer cases, a relatively small proportion. All available research suggests that the mechanism of development of these cancers is very different to that of epithelial cancers. Related to this is the fact that they occur in completely different demographics. One subgroup of particularly mysterious sarcomas is associated with the presence of fusion genes in the tumour population. As the name suggests, fusion genes are the result of two separate genes fusing together to form a novel gene and protein. The process alters the functions of the original genes, sometimes with drastic consequences. When this occurs in key regulatory genes, normal cellular gene expression can be altered. This, in turn, can lead to the breakdown of the normal checkpoints in the cell cycle that are a regular part of stopping cancer. Dr Takuro Nakamura of the Cancer Institute, part of the Japanese Foundation for Cancer Research and his lab are working on uncovering the how these sarcomas develop. Nakamura elaborates on his aims for his work: 'we will investigate the biological nature of bone and soft tissue sarcoma (BSTS), its carcinogenesis process and genetic network important for sarcomagenesis and malignant progression. The anti-tumour effects of drugs and low molecular weight inhibitors will be tested using the models as platforms to explore novel therapies.' Fusion gene-associated sarcomas (FGAS) are still relatively poorly characterised. In fact, it is even unclear which cells in the tissue are most often responsible for the beginnings of the disease. Because of this, it is difficult to identify uniquely or abnormally expressed proteins or marker. This, in turn, means it has been very difficult to identify molecular targets for drugs and therefore molecular target therapies are underdeveloped compared to other fields of cancer. Nakamura and his team are tackling the issue from several different angles in order to uncover these answers. They have discovered two novel fusion genes that appear to have a significant role in certain FGASs.