this comment was about different tumour genome work, but it could apply just as well to the Gerlinger article…
Jim Woodgett said:
Are these findings surprising given the well understood nature of the instability of tumour genetic integrity? Once tumours have sufficiently compromised their DNA repair processes, their rates of mutation are significantly elevated and heterogeneity is bound to increase. We also know that selective pressure (acquisition of drug resistance) can cause watershed shifts in cell populations, allowing new populations to emerge and dominate. Tracking these shifts should yield important prognostic information, unless genomic integrity is shot, at which point using precision tools is likely a wasted effort. Expansion of deep sequencing of genetically unstable tumours will undoubtedly generate reams of data. However, documenting the precise shapes of clouds on one day does not help predict the shapes the following day, or the next.