Doomed from the TERT? A Two-Stage Model of Tumorigenesis in IDH-Wild-Type Glioblastoma.

Using longitudinal molecular profiling, Körber et al. propose in this issue of Cancer Cell that IDH-wild-type glioblastomas initiate years pre-diagnosis with chromosome-level alterations that drive cell proliferation but require survival-promoting mutations, commonly in the TERT promoter, to form a detectable tumor. Multiple subclones drive disease progression, creating a therapeutic challenge.