b'Gel & Capillary | CE-IVD Assays IGH + IGK B-Cell Clonality AssaysGel and CapillaryAssaysIGH + IGK B-Cell Clonality AssaysAssay Description A single thermal cycler program and similar detection methodologies are The IdentiClone IGH + IGK B-Cell Clonality Assays are in vitro used with all of our Gene Clonality Assays. This improves consistency and diagnostic products intended for PCR-based detection of clonalfacilitates cross-training on a broad range of different assays.immunoglobulin heavy chain and kappa light chain genePerformance Characteristicsrearrangements in patients with suspect lymphoproliferations.Specifically, the IdentiClone IGH + IGK B-Cell Clonality Assays can beData from two independent studies that tested more than 300 patient used to: samples of varying types suggests the diagnostic accuracyof selected IdentiClone tests to be 96%. In both peer-reviewed Identify clonality in atypical lymphoproliferative disorders studies, there were no clear false-positive results generated using the Support a differential diagnosis between reactive lesions andIdentiClone tests, and there was a high level of precision. 2 The clinico-histopathological diagnosis correlated well with PCR hematologic malignancies results in a higher number of patients when compared with Southern Assign presumptive lineage in mature monoclonal Blot (SB) results, as seen below: lymphoproliferative disordersPCR/SB concordance: 1 dentify tumor-specific markers (IGH and IGK geneI IGH:93% sensitivity / 92% specificityrearrangements) for post-treatment monitoring IGK: 90% sensitivity / 90% specificity Monitor and evaluate disease recurrence IGL: 86% sensitivity / 92% specificity TRB: 86% sensitivity / 98% specificitySummary and Explanation of the Test TRG: 89% sensitivity / 94% specificity TRD: 83% sensitivity / 95% specificityThe Invivoscribe CE-marked IdentiClone Assays represent a uniquePCR vs. SB analysis relative to histopathology and final diagnosis:approach to PCR-based clonality testing. These standardized assays were carefully optimized, testing positive and negative controlPCR/SB concordance: 2PCR sensitivity: SB sensitivity: samples using multiplex master mixes. Assay development wasIGH + IGK: 85% 98% 39% followed by extensive validation including the testing of more thanTRB: 85% 96% 35%400 clinical samples using Revised European/American Lymphoma (REAL) Classification. Testing was done at more than thirty prominent independent testing centers throughout Europe in a collaborative studyReferenceknown as the BIOMED-2 Concerted Action. Results from this BIOMED-2 1 1. JJM van Dongen et al., Leukemia 17:2257-2317 (2003). study appear in Leukemia, a leading peer-reviewed journal.2. Y Sandberg et al., J. Mol. Diag. 7(4):495-503 (2005). These kits include six master mixes to test for rearrangements of3. Van Krieken, JHJM et al., Leukemia 21:201 - 206 (2007).both IGH and IGK. The IGH Tube A, B, and C master mixes target the framework 1, 2, 3 regions (respectively) within the variable (V H ) region, and the joining (J H ) region of the immunoglobulin heavy chain locus. The IGK Tube A master mix targets the variable (V) and the joining (J) region. IGK Tube B master mix targets kappa deleting element (K de ) rearrangements with the variable (V) region and the intragenic J-C region. The resulting V-K deand J-C intron-K derearrangements are aresult of unsuccessful rearrangements retained by the B cell. For best sensitivity, it is recommended to test suspect B-cell malignancies for 3 Figure Legend: Simple representation of the organization of a rearranged both IGH and IGK.The included Specimen Control Size Ladder mastermix targets multiple genes and generates a series of amplicons ofimmunoglobulin heavy chain (IGH) gene on chromosome 14q32.33 and the immunoglobulin kappa light chain gene on chromosome 2p11.2. Black arrows approximately 100, 200, 300, 400, and 600 base pairs to ensure that therepresent the relative positions of primers that target the conserved framework quality and quantity of input DNA is adequate to yield a valid result. regions (FR1-3) and the downstream consensus J Hgene segments for IGH and the V, J, INTR and Kde primers which are included in the IGK master mix tubes.This assay is based on the EuroClonality/BIOMED-2 Concerted Action BMH4-CT98-3936.58'