Translating a gene expression signature for multiple myeloma prognosis into a robust high-throughput assay for clinical use

Abstract

Background: Widespread adoption of genomic technologies in the management of heterogeneous indications, including Multiple Myeloma, has been hindered by concern over variation between published gene expression signatures, difficulty in physician interpretation and the challenge of obtaining sufficient genetic material from limited patient specimens. Methods. Since 2006, the 70-gene prognostic signature, developed by the University of Arkansas for Medical Sciences (UAMS) has been applied to over 4,700 patients in studies performed in 4 countries and described in 17 peer-reviewed publications. Analysis of control sample and quality control data compiled over a 12-month period was performed. Results: Over a 12 month period, the 70-gene prognosis score (range 0-100) of our multiple myeloma cell-line control sample had a standard deviation of 2.72 and a coefficient of variance of 0.03. The whole-genome microarray profile used to calculate a patient's GEP70 score can be generated with as little as 15 ng of total RNA; approximately 30,000 CD-138+ plasma cells. Results from each GEP70 analysis are presented as either low (70-gene score <45.2) or high (≥45.2) risk for relapse (newly diagnosed setting) or shorter overall survival (relapse setting). A personalized and outcome-annotated gene expression heat map is provided to assist in the clinical interpretation of the result. Conclusions: The 70-gene assay, commercialized under the name 'MyPRS®' (Myeloma Prognostic Risk Score) and performed in Signal Genetics' CLIA-certified high throughput flow-cytometry and molecular profiling laboratory is a reproducible and standardized method of multiple myeloma prognostication. © 2014 van Laar et al.; licensee BioMed Central Ltd.