Identification and validation of biomarkers of IgV(H) mutation status in chronic lymphocytic leukemia using microfluidics quantitative real-time polymerase chain reaction technology.

2007: LVAbruzzo; KAnderson; LLBarron; KRCoombes; AFerrajoli; DJones; MJKeating; MLuthra; RLuthra; RJNewman; SO'Brien; STalwalkar; WGWierda;

J Mol Diagn.2007;9(4):546-55.

NLM PMID: 17690214

Article abstract

To develop a model incorporating relevant prognostic biomarkers for untreated chronic lymphocytic leukemia patients, we re-analyzed the raw data from four published gene expression profiling studies. We selected 88 candidate biomarkers linked to immunoglobulin heavy-chain variable region gene (IgV(H)) mutation status and produced a reliable and reproducible microfluidics quantitative real-time polymerase chain reaction array. We applied this array to a training set of 29 purified samples from previously untreated patients. In an unsupervised analysis, the samples clustered into two groups. Using a cutoff point of 2% homology to the germline IgV(H) sequence, one group contained all 14 IgV(H)-unmutated samples; the other contained all 15 mutated samples. We confirmed the differential expression of 37 of the candidate biomarkers using two-sample t-tests. Next, we constructed 16 different models to predict IgV(H) mutation status and evaluated their performance on an independent test set of 20 new samples. Nine models correctly classified 11 of 11 IgV(H)-mutated cases and eight of nine IgV(H)-unmutated cases, with some models using three to seven genes. Thus, we can classify cases with 95% accuracy based on the expression of as few as three genes.

Research Topics
• Diseases
   Leukemia, Lymphocytic, Chronic, B-Cell

Title and Abstract from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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Last MEDLINE®/PubMed® update: 1st of December 2015