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.
Public Health Relevance: Successful cancer treatment begins with an accurate diagnosis. Generally, cancer diagnosis involves a pathologist trained to distinguish between characteristics of healthy tissues and cells from those that are diseased. Based on the diagnosis, a multidisciplinary team determines the optimal therapy for the patient. Erroneous diagnosis of cancer can lead to inappropriate and potentially damaging treatments. Furthermore, early intervention is critical to successful treatment of cancer patients, emphasizing the importance of a correct diagnosis at the earliest possible time. Several biomarkers have been discovered that are unique to specific types of tumors. The use of these biomarkers has helped distinguish between tumors with similar physical characteristics, yet of different origins that require significantly different treatments. Tests that can accurately identiy these biomarkers enable pathologists to make definitive diagnosis that helps physicians decide on the most appropriate therapy.
Public Health Relevance Statement: Successful cancer treatment begins with an accurate diagnosis. Generally, cancer diagnosis involves a pathologist trained to distinguish between characteristics of healthy tissues and cells from those that are diseased. Based on the diagnosis, a multidisciplinary team determines the optimal therapy for the patient. Erroneous diagnosis of cancer can lead to inappropriate and potentially damaging treatments. Furthermore, early intervention is critical to successful treatment of cancer patients, emphasizing the importance of a correct diagnosis at the earliest possible time. Several biomarkers have been discovered that are unique to specific types of tumors. The use of these biomarkers has helped distinguish between tumors with similar physical characteristics, yet of different origins that require significantly different treatments. Tests that can accurately identiy these biomarkers enable pathologists to make definitive diagnosis that helps physicians decide on the most appropriate therapy.
NIH Spending Category: Biotechnology; Cancer; Genetics; Pediatric; Pediatric Research Initiative; Rare Diseases
Project Terms: base; beta-2 Microglobulin; Biological Assay; Biological Markers; cancer diagnosis; Cancer Patient; cancer therapy; Cell Line; Cells; Characteristics; Chromosomal translocation; Clinical Sensitivity; cost; design; Detection; Development; Diagnosis; Diagnostic; Differentiation Antigens; DNA-Directed DNA Polymerase; Early treatment; Ensure; Ewings sarcoma; Family; FLI1 gene; Fluorescent Probes; fluorophore; Functional RNA; fusion gene; Gene Targeting; Genes; Genetic screening method; Goals; Histocompatibility Testing; Histologic; Hydrolysis; Lead; Los Angeles; medical schools; Methodology; Methods; Microarray Analysis; Molecular; Molecular Genetics; multidisciplinary; neoplastic cell; Oligonucleotide Primers; Pathologist; Patients; Pediatric Hospitals; Performance; Physicians; Polymerase Chain Reaction; prevent; Property; Reaction; Recurrence; relating to nervous system; Research Personnel; RNA; RNA Splicing; Sampling; Sensitivity and Specificity; Signal Transduction; Technology; Testing; Time; Tissues; Training; Transcript; transcription factor; tumor; Tumor Tissue; Tumor-Derived; Validation; Variant
