Longitudinal Molecular Trajectories of Diffuse Glioma in Adults

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear ¹² . Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of difuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specifc gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at diferent rates across the glioma subtypes, and hypermutation was not associated with diferences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner

Amplitude and frequency variability of the pulsating DB white dwarf stars KUV 05134+2605 and PG 1654+160 observed with the Whole Earth Telescope

WOS: 000182039700036We have acquired new time series photometry of the two pulsating DB white dwarf stars KUV 05134+2605 and PG 1654+160 with the Whole Earth Telescope. Additional single-site photometry is also presented. We use all these data plus all available archival measurements to study the temporal behaviour of the pulsational amplitudes and frequencies of these stars for the first time. We demonstrate that both KUV 05134+2605 and PG 1654+160 pulsate in many modes, the amplitudes of which are variable in time; some frequency variability of PG 1654+160 is also indicated. Beating of multiple pulsation modes cannot explain our observations; the amplitude variability must therefore be intrinsic. We cannot find stable modes to be used for determinations of the evolutionary period changes of the stars. Some of the modes of PG 1654+160 appear at the same periods whenever detected. The mean spacing of these periods (approximate to40 s) suggests that they are probably caused by non-radial gravity-mode pulsations of spherical degree l = 1. If so, PG 1654+160 has a mass around 0.6 M.. The time-scales of the amplitude variability of both stars (down to two weeks) are consistent with theoretical predictions of resonant mode coupling, a conclusion which might however be affected by the temporal distribution of our data