Researchers at the Wellcome Sanger Institute, EMBL-EBI, Open Target, GSK, and their collaborators have made the first large-scale analysis of cancer gene fusions that result from the merging of two previously separate genes. Now, the team has used CRISPR to uncover which gene fusions are critical for the growth of cancer cells. Also identified by the researchers is the new gene fusion that presents a new drug target for multiple cancers like the brain and ovarian cancers.
The team published the result of the research in Nature Communication to provide more certainty for the use of specific gene fusions to diagnose and guide the treatment of patients. Also, in the study, there was a suggestion of repurposing the existing drugs to treat some people with pancreatic, breast, and lung cancers based on the gene fusions discovered in their tumors.
The abnormal joining of two otherwise different genes is the cause of gene fusions, and gene fusions play an essential role in the development of cancer. Scientists use them as a diagnostic tool 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. Also, they are also the targets of some of the latest targeted treatments for cancer.
So far, researchers have identified around 20,000 gene fusions. However, their specific function and role in developing cancer remain poorly understood, discriminating between fusions that have a role in cancer survival and those that do not have important clinical implications.
They 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 vital gene fusions are critical for cancer cell survival. In their findings, 90 percent of gene fusions do not play an essential role in cancer. These results should be considered when inferring causes of cancer from the genome sequence of patients' tumors.
Co-first author of the study from the Wellcome Sanger Institute, Dr. Gabriele Picco said that the majority of gene fusions are not essential for the survival of cancer cells. As genome sequencing patients' tumor becomes more prevalent, those interpreting the data must be careful when considering whether a particular gene fusion is driving cancer.
Also, the team found a new fusion, YAP1-MAML2, which is critical for the progression of multiple cancer types such as the brain and ovarian cancers.
Lead author of the study from the Wellcome Sanger Institute and Open Targets, Dr. Mathew Garnett said that they found a handful of gene fusions that are vital for cancer survival. These genetic changes may present opportunities for treating patients with existing drugs or could be the drug targets of the future. Also, they considered a new gene fusion, YAP-MAML2, which provides a new drug target for several cancers, including ovarian cancer.
