Detection of circulating tumour cell clusters in human glioblastoma.
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Date
2018-08-14Author
Krol, I
Castro-Giner, F
Maurer, M
Gkountela, S
Szczerba, BM
Scherrer, R
Coleman, N
Carreira, S
Bachmann, F
Anderson, S
Engelhardt, M
Lane, H
Evans, TRJ
Plummer, R
Kristeleit, R
Lopez, J
Aceto, N
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Animals
Humans
Mice
Glioblastoma
Brain Neoplasms
Disease Progression
Oxadiazoles
Benzimidazoles
Cell Count
Cluster Analysis
Xenograft Model Antitumor Assays
Mutation
Female
Male
Gene Regulatory Networks
Neoplastic Cells, Circulating
Genetic Variation
Whole Exome Sequencing
Research team
Medicine (de Bono Prostate)
Molecular Addictions
Cancer Biomarkers
Language
eng
Date accepted
2018-06-25
License start date
2018-08
Citation
British journal of cancer, 2018, 119 (4), pp. 487 - 491
Publisher
NATURE PUBLISHING GROUP