Spatiotemporal Evolution of the Primary Glioblastoma Genome

Cancer Cell. 2015 Sep 14;28(3):318-28. doi: 10.1016/j.ccell.2015.07.013.

Abstract

Tumor recurrence following treatment is the major cause of mortality for glioblastoma multiforme (GBM) patients. Thus, insights on the evolutionary process at recurrence are critical for improved patient care. Here, we describe our genomic analyses of the initial and recurrent tumor specimens from each of 38 GBM patients. A substantial divergence in the landscape of driver alterations was associated with distant appearance of a recurrent tumor from the initial tumor, suggesting that the genomic profile of the initial tumor can mislead targeted therapies for the distally recurred tumor. In addition, in contrast to IDH1-mutated gliomas, IDH1-wild-type primary GBMs rarely developed hypermutation following temozolomide (TMZ) treatment, indicating low risk for TMZ-induced hypermutation for these tumors under the standard regimen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / therapeutic use
  • Brain Neoplasms / drug therapy
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics*
  • Glioma / genetics
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics*
  • Temozolomide

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • Temozolomide

Associated data

  • GEO/GSE63035