Sensitivity

For most T-cell lymphomas and acute lymphoblastic leukemias, TCR gene rearrangement studies are the only molecular assays available. The sensitivity of these assays varies. SBA remains the gold standard for TCR rearrangement testing because, in principle, all rearrangements can be detected. SBA, however, has a sensitivity of approximately 1% to 5%. Most PCR-based assays detect only ~80%

of TCR rearrangements compared to SBA because PCR is primer dependent. However, application of multiple TCRG primer sets allows the detection of the vast majority of rearrangements.21 Patient-specific primers have been developed on a research basis and allow a lower level of detection (around 0.001%), but this approach is laborintensive and time-consuming, thus prohibitive for wide clinical application. Due to the great diversity in possible rearrangements, the vast majority of PCR tests use consensus primers, reaching a sensitivity of around 0.1% to 1% (in the absence of a prominent polyclonal background and depending on the method used for analysis of the PCR products). TCR gene rearrangements may remain obscure if the locus under investigation has been deleted in the rearrangement, or has remained in the germline configuration. It is also possible that the primer binding site itself was removed or changed during the rearrangement. Moreover, false-negative results may be caused by an insufficient number of clonal cells in the sample. For MRD testing using PCR, the level of detection varies markedly based on the test method and the exact molecular basis of the lym-phoid proliferation.

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