title: Identification and validation of biomarkers of IgV(H) mutation status in chronic lymphocytic leukemia using microfluidics quantitative real-time polymerase chain reaction technology.
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.
authors: University of Texas M.D. Anderson Cancer Center, Department of Hematopathology, Box 72, 1515 Holcombe Blvd., Houston, TX 77030, USA. labruzzo@mdanderson.org
authors: Lynne V
authors: LV
authors: Abruzzo
authors: Lynn L
authors: LL
authors: Barron
authors: Keith
authors: K
authors: Anderson
authors: Rachel J
authors: RJ
authors: Newman
authors: William G
authors: WG
authors: Wierda
authors: Susan
authors: S
authors: O'brien
authors: Alessandra
authors: A
authors: Ferrajoli
authors: Madan
authors: M
authors: Luthra
authors: Sameer
authors: S
authors: Talwalkar
authors: Rajyalakshmi
authors: R
authors: Luthra
authors: Dan
authors: D
authors: Jones
authors: Michael J
authors: MJ
authors: Keating
authors: Kevin R
authors: KR
authors: Coombes
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D044085:Microfluidics / Q000379:methods*; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region
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