Clinical validation of the SureDx EFT diagnostic test

Entrogen, Inc., Woodland Hills CA

Investigators

Abstract

DESCRIPTION (provided by applicant): Development of a diagnostic biomarker for Ewing's Sarcoma family of tumors Ewing's family tumors (EFTs) are characterized by recurrent chromosomal translocations that produce chimeric fusions between the EWS gene and one of five ETS transcription factors. The expression of EWS/FLI1, the predominant fusion product in EFTs, is believed to deregulate downstream target genes in an undefined tissue type and leads to development of EFTs. Histologically, EFTs are characterized as small, round-blue cells, displaying some neural differentiation markers that suggest neuroectodermal origin. However, it is difficult to make an accurate diagnosis based on the physical characteristics of EFT cells, because of similarities with other small, round-blue cell tumors. Additionally, while multiple splice variants of the fusion genes have been found in EFTs, to date, no single biomarker has been identified that can distinguish between EFTs and other small, round-blue cell tumors. Researchers at the USC Keck School of Medicine/Children's Hospital of Los Angeles have identified a non-coding RNA that is uniquely expressed in EFTs. In their studies, the use of this biomarker distinguished Ewing's tumors and EFT derived cell lines from other small round-blue cell tumors. Expression of this non-coding RNA was not found in other healthy or tumor tissues. These findings suggest that the use of this biomarker can help with a definite diagnosis of EFTs. EntroGen Inc proposes to develop a quantitative molecular genetic test to detect the expression of AK057037 RNA transcript in tumor tissues suspected to be EFTs. This assay will be based on fluorescent hydrolysis probes that allow for simultaneous detection of both AK057037 and endogenous gene (control) transcripts in a single reaction well. This will reduce the amount of time, labor and cost required to perform the test and enable rapid and accurate analysis of the results. Furthermore, this would enable physicians to treat EFT and non-EFT patients with appropriate therapies.