Abstract
BackgroundWidespread 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.MethodsSince 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.ResultsOver 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.ConclusionsThe 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.
Highlights
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
In this paper we describe the use of a high-throughput process, combining cell isolation, flow cytometry and gene expression profiling to provide physicians with personalized prognostic assessments of multiple myeloma, using bone marrow aspirate, based on the comprehensively validated GEP70 signature
Interpretation of GEP70 score using personalized gene expression heat maps The GEP70 risk score for each MyPRS analysis performed was visualized by creation of a personalized twodimensional heat map generated by the ResultsPXTM genomic data management platform developed by Signal Genetics. This system uses Microsoft SQL Server (Redmond, WA) databases, R [25] and Bioconductor [26] and custom scripts to display the expression profile of Genomic profiling of paired aliquots of patient CD138+ cells in research and clinical laboratories shows high correlation of GEP70 scores Ninety-nine patient bone marrow aspirate specimens were split into two aliquots and processed as described in both the University of Arkansas for Medical Sciences (UAMS) research laboratory and at Signal Genetics’ CLIA-certified laboratory (Figure 1)
Summary
Plasma cell quantification and separation Processing of bone marrow aspirate specimens submitted for MyPRS® analysis occurs largely as previously described [23]. Diagnosed multiple myeloma patients treated with high-dose melphalan and stem cell transplant [12]. Interpretation of GEP70 score using personalized gene expression heat maps The GEP70 risk score for each MyPRS analysis performed was visualized by creation of a personalized twodimensional heat map generated by the ResultsPXTM genomic data management platform developed by Signal Genetics. This system uses Microsoft SQL Server (Redmond, WA) databases, R [25] and Bioconductor [26] and custom scripts to display the expression profile of
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