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Available from: Flore Delalande, Jul 19, 2015
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    ABSTRACT: In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11;14) and t(14;18). This has resulted in 107 different primers in only 18 multiplex PCR tubes: three VH-JH, two DH-JH, two Ig kappa (IGK), one Ig lambda (IGL), three TCR beta (TCRB), two TCR gamma (TCRG), one TCR delta (TCRD), three BCL1-Ig heavy chain (IGH), and one BCL2-IGH. The PCR products of Ig/TCR genes can be analyzed for clonality assessment by heteroduplex analysis or GeneScanning. The detection rate of clonal rearrangements using the BIOMED-2 primer sets is unprecedentedly high. This is mainly based on the complementarity of the various BIOMED-2 tubes. In particular, combined application of IGH (VH-JH and DH-JH) and IGK tubes can detect virtually all clonal B-cell proliferations, even in B-cell malignancies with high levels of somatic mutations. The contribution of IGL gene rearrangements seems limited. Combined usage of the TCRB and TCRG tubes detects virtually all clonal T-cell populations, whereas the TCRD tube has added value in case of TCRgammadelta(+) T-cell proliferations. The BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well as for the identification of PCR targets suitable for the detection of minimal residual disease.
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    ABSTRACT: To determine a possible role of aberrant somatic hypermutation (ASHM) in the pathogenesis of thyroid lymphoma (TL), mutational status of genes affected by ASHM, including c-MYC, PIM-1, PAX-5 and RhoH/TTF, was analyzed. Tumor specimens from 33 patients with thyroid B-cell lymphoma and 14 with chronic lymphocytic thyroiditis (CLTH), an autoimmune thyroiditis known to provide a basis for TL development, was examined. Mutations of at least one of these genes was detected in 16 of 33 (48.5%) patients with TL and in 2 of 14 (14.3%) CLTH. Occurrence of ASHM in PIM-1, RhoH/TTF, and c-MYC was a constant finding in follicular lymphoma (FL) (all of 11 cases) but not so frequent in diffuse large B-cell lymphoma (DLBCL) (4 (33.3%) of 12 cases) and Marginal zone B-cell lymphoma (MZBCL) (1 (10.0%) of 10 cases). ASHM activity is ongoing in most of FL and DLBCL because intraclonal variants were found. FL was also unique in its lower expression level of activation-induced cytidine deaminase, a main player in DNA-modifying processes during SHM, compare to DLBCL and MZBCL.
    Leukemia research 12/2008; 33(5):649-54. DOI:10.1016/j.leukres.2008.10.007 · 2.69 Impact Factor