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C. Brieghel et al.
er, recommend using a cell line harboring a rare TP53mut predicted to encode functional p53, such as BRG-A (TP53:c.1060C>G), to avoid both risk of contamination and risk of omitting significant low burden mutations.34 We successfully achieved an LOD of 0.3% VAF, applied in previous studies of minor TP53muts,13,14,18 and could even lower the LOD to 0.2% VAF. As we were unable to prove any impact on newly diagnosed patients with IGHV-M, our results support the current guidelines recommending TP53 assessment only prior to treatment.12
This study furthers the identification of a clinically sig- nificant LOD for TP53muts in CLL. The method proposed here for analysis of minor TP53muts warrants validation across laboratories for a standard technical LOD for TP53muts. Subsequent validation and standardization of TP53 mutation assays within networks such as the European Research Initiative on CLL (ERIC, http://ericll.org) may provide the platform needed for collaborative multi- center analyses seeking to define a validated clinical LOD for TP53muts.
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