Characterization of IGH locus breakpoints in multiple myeloma indicates a subset of translocations appear to occur in pregerminal center B cells.

Translocations in myeloma are thought to occur solely in mature B cells in the germinal center through class switch recombination (CSR). We used a targeted captured technique followed by massively parallel sequencing to determine the exact breakpoints in both the immunoglobulin heavy chain (IGH) locus and the partner chromosome in 61 presentation multiple myeloma samples. The majority of samples (62%) have a breakpoint within the switch regions upstream of the IGH constant genes and are generated through CSR in a mature B cell. However, the proportion of CSR translocations is not consistent between cytogenetic subgroups. We find that 100% of t(4;14) are CSR-mediated; however, 21% of t(11;14) and 25% of t(14;20) are generated through DH-JH recombination activation gene-mediated mechanisms, indicating they occur earlier in B-cell development at the pro-B-cell stage in the bone marrow. These 2 groups also generate translocations through receptor revision, as determined by the breakpoints and mutation status of the segments used in 10% and 50% of t(11;14) and t(14;20) samples, respectively. The study indicates that in a significant number of cases the translocation-based etiological events underlying myeloma may arise at the pro-B-cell hematological progenitor cell level, much earlier in B-cell development than was previously thought.

Series-L/parallel-tuned Class-E power amplifier analysis

An analysis of the operation of a new series-L/parallel-tuned Class-E amplifier and its equivalence to the classic shunt-C/series-tuned Class-E amplifier are presented. The first reported closed form design equations for the series-L/parallel-tuned topology operating under ideal switching conditions are given, including the switch current and voltage in steady state, the circuit component values, the peak values of switch current and voltage and the power-output capability. Theoretical analysis is confirmed by numerical simulation for a 500 mW (27 dBm), 10% bandwidth, 5 V series-L/parallel-tuned, then, shunt-C/series-tuned Class-E power amplifier, operating at 2.5 GHz. Excellent agreement between theory and simulation results is achieved.