In the first large-scale analysis of cancer gene fusions, which result from the merging of two previously separate genes, researchers at the Wellcome Sanger Institute, EMBL-EBI, Open Targets, GSK and their collaborators have used CRISPR to uncover which gene fusions are critical for the growth of cancer cells. The team also identified a new gene fusion that presents a novel drug target for multiple cancers, including brain and ovarian cancers. The results, published today (16 May) in Nature Communications, give more certainty for the use of specific gene fusions to diagnose and guide the treatment of patients. Researchers suggest existing drugs could be repurposed to treat some people with pancreatic, breast and lung cancers, based on the gene fusions found in their tumours.
Gene fusions, caused by the abnormal joining of two otherwise different genes, play an important role in the development of cancer. They are currently used as diagnostic tools to predict how particular cancer patients will respond to drugs, as well as prognostics, to estimate the outcome for a patient given the best possible care. They are also the targets of some of the latest targeted treatments for cancer. Researchers have identified around 20,000 gene fusions so far, however their exact function and role in developing cancer remains poorly understood. Discriminating between fusions that have a role in cancer survival and those that do not has important clinical implications. In the first large-scale study of gene fusion function, researchers at the Wellcome Sanger Institute, EMBL-EBI, Open Targets, GSK and their collaborators analysed more than 8,000 gene fusions in over 1,000 human cancer cell lines, from 43 different cancer types, including paediatric cancers and cancers with unmet clinical need. The team tested the cell lines against more than 350 anti-cancer drugs to see which existing drugs could be repurposed to potentially treat cancer patients with gene fusions, and employed CRISPR as a tool to discover which key gene fusions are critical for cancer cell survival.