Detection of circulating tumour cell clusters in human glioblastoma.
Ilona KrolFrancesc Castro-GinerMartina MaurerSofia GkountelaBarbara Maria SzczerbaRamona ScherrerNiamh ColemanSuzanne CarreiraFelix BachmannStephanie AndersonMarc EngelhardtHeidi LaneThomas Ronald Jeffry EvansRuth PlummerRebecca KristeleitJuanita LopezNicola AcetoPublished in: British journal of cancer (2018)
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.
Keyphrases
- circulating tumor cells
- induced apoptosis
- endothelial cells
- circulating tumor
- cell cycle arrest
- end stage renal disease
- single cell
- ejection fraction
- chronic kidney disease
- copy number
- physical activity
- dna damage
- newly diagnosed
- cell death
- induced pluripotent stem cells
- papillary thyroid
- peritoneal dialysis
- case report
- white matter
- oxidative stress
- squamous cell carcinoma
- mental health
- dna repair
- bone marrow
- young adults
- brain injury
- pi k akt