Gene fusions, or chromosomal translocations, are a common type of mutation where pieces of DNA from two different genes are attached together. The mutations are known to be common in blood cancers and have recently been found to also exist in solid tumors. Researchers at the Mayo Clinic have developed an RNA sequencing assay that successfully detected 93% of gene fusions that had been identified by other techniques. In addition, the next-gen assay detected 18 fusions that were previously unknown. The study was published in The Journal of Molecular Diagnostics.
RNA sequencing, commonly known as RNA-Seq, is a technique to analyze expression profiles of thousands of genes at one time in a single cell. The research team is exploring the potential to use RNA-Seq in a clinical setting to diagnose disease and to determine optimal therapeutic treatments. "It is very important to understand the accuracy, reproducibility, and sensitivity of these assays for utilities such as gene fusion detection before they are used clinically. To date very few studies have done that," explained lead investigator Kevin C. Halling, MD, PhD, of the Departments of Laboratory Medicine and Pathology at the Mayo Clinic.
The study included 76 samples made up of 61 tumor specimens and 15 normal tissues. Established methods such as RT-PCR and Sanger sequencing methods were used to identify gene fusions. The assay measured fusions in 571 genes known to have a role in solid tumor formation. The RNA-seq assay successfully identified 38 of 41 gene fusions confirmed by established methods and also detected 22 fusions in 17 tumors that had not been previously detected. Interesting, 18 of the fusions were completely unknown until now.
The results of the study demonstrate that RNA-seq is a viable technique for detecting gene fusions and appears to be more sensitive than existing methods. The discovery of new mutations could lead to improved targeted therapies for cancer sufferers.