Detection of circulating tumour cell clusters in human glioblastoma

Br J Cancer. 2018 Aug;119(4):487-491. doi: 10.1038/s41416-018-0186-7. Epub 2018 Aug 1.

Abstract

Human glioblastoma (GBM) is a highly aggressive, invasive and hypervascularised malignant brain cancer. Individual circulating tumour cells (CTCs) are sporadically found in GBM patients, yet it is unclear whether multicellular CTC clusters are generated in this disease and whether they can bypass the physical hurdle of the blood-brain barrier. Here, we assessed CTC presence and composition at multiple time points in 13 patients with progressing GBM during an open-label phase 1/2a study with the microtubule inhibitor BAL101553. We observe CTC clusters ranging from 2 to 23 cells and present at multiple sampling time points in a GBM patient with pleomorphism and extensive necrosis, throughout disease progression. Exome sequencing of GBM CTC clusters highlights variants in 58 cancer-associated genes including ATM, PMS2, POLE, APC, XPO1, TFRC, JAK2, ERBB4 and ALK. Together, our findings represent the first evidence of the presence of CTC clusters in GBM.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / pharmacology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cell Count
  • Cluster Analysis
  • Disease Progression
  • Female
  • Gene Regulatory Networks / drug effects
  • Genetic Variation
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Male
  • Mice
  • Mutation
  • Neoplastic Cells, Circulating / chemistry
  • Neoplastic Cells, Circulating / drug effects
  • Neoplastic Cells, Circulating / pathology*
  • Oxadiazoles / administration & dosage*
  • Oxadiazoles / pharmacology
  • Whole Exome Sequencing
  • Xenograft Model Antitumor Assays

Substances

  • BAL101553
  • Benzimidazoles
  • Oxadiazoles