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Qi Zhang MD PhD FRCPC
Neuropathologist and Assistant Professor
London Health Sciences Centre and Western University
London, Ontario, Canada
Presentation to C4G research group
• Why bank brain tumour tissues?
• How did the BTTB evolve?
• Where is the BTTB, how do samples end up there, how are they stored, and who does the work.
• How do we ensure high quality samples?
• Summary of cases banked and tissues released for research in the last decade
• How do researchers obtain tissue for their work?
• How much does it all cost?
• Frozen tissue– Widely needed for research:
• Formalin-fixed tissue being used more frequently for molecular biology research
– Not systematically stored in some/many hospitals?• Under investigation
– Samples not available for basic sciences departments without hospital affiliation
• Batching– Ad hoc collection of a set of a given tumour type may take months
to years
– BTTB allows a batch of a specified tumour to be supplied to researchers within a few days
• Allows preliminary surveys of research questions
• Not very useful for treatment trial work in which samples and patients have to be linked
• Systematic quality control
• No tissue possessiveness
• Developed in late 1980s (Dr. R. Del Maestro)
• Initially for local brain tumour research laboratory
• Gradual evolution to an international resource for brain
tumour researchers
– Local funding: Knight’s of Columbus, families, London Brain
Tumour Foundation, Victoria Hospital Research Fund
– National Cancer Institute of Canada (1994-1997)
– Brain Tumour Foundation of Canada (1998 to Present)
– London Health Sciences Centre
• Pathology and CNS Departments
• Adults – 1536
– Mainly primary brain tumours, meningiomas and
metastases (more data when reviewing current
stock)
• Children (0-18 years of age) – 669
– Includes pilocytic astrocytomas (53),
medulloblastomas (32), ependymomas (27),
glioblastomas (18), ATRT (8), PNET (4),
meningiomas (5) and metastases (3)
Where is the BTTB?
• University Hospital, London Health Sciences Centre (LHSC)
• Conceptually part of the LHSC Pathology Department
• Clinical Neurosciences floor
• https://www.braintumour.ca/research/brain-tumour-tissue-bank/
• Small biopsies (stereotactic) are not banked
• Most large samples are banked
• Automatic (Pathology Department)
• Bank Co-Ordinator ‘on-call’ for samples
• Standard operative consent then later specific
consent
• ‘Delinkage’, anonymity
Who Does the Work?
• Everyone, in various ways: patient, family,
neurosurgeon, nurses, researchers, BTFC
staff, neuropathologists
• The Bank Co-Ordinator is essential
• (Marcela White)
• Codirectors:– Dr. J. Megyesi (Neurosurgeon, London)
– Dr. Q. Zhang (Neuropathologist, London)• 2020 – present
– Dr. D. A. Ramsay (Neuropathologist, retired)• 1995 - 2020
• Annual report to BTFC:– Detailed summary of operations for the year
– Much of the data in this presentation comes from these reports
How do Researchers Obtain Brain
Tumour Samples?
• Standard application form
• Assessed by Co-Directors
• Shipping and other charges reclaimed
• Researchers are asked:– To reimburse the shipping expenses
– To make a pro rata donation directly to the BTFC
– To acknowledge the support of the BTFC in scientific
publications
• There are various types of samples available from 1943 cases (banked from 1995 to the present):– approximately 3 vials per case (not including paraffin
blocks)
• Examples of tumours available:– Primary CNS tumours - 713
• e.g., glioblastomas (307), oligodendrogliomas (25), ependymomas (25), pilocytic astrocytoma (20), medulloblastomas (17), PXAs (10)
– Meningeal tumours - 229 • meningioma (223), haemangiopericytoma (6)
– Metastases - 285 • e.g., lung (111), breast (25), colon (15), melanoma (27),
kidney 3
Examples of Recent Publications that
have Used BTTB Material
• Johnson H, White FM et al 2014 Quantitative analysis of signaling networks across differentially embedded
tumors highlights interpatient heterogeneity in human glioblastoma, J Proteome Res. 2014 Nov 7;13(11):4581-
93.doi: 10.1021/pr500418w.Epub
• Lubanska D, Porter LA et al 2014 The cyclin-like protein Spy1 regulates growth and division characteristics of
the CD133+ population in human glioma, Cancer Cell 13;25(1):64-76
• Bellail AC, Olson JJ, Hao C.2014, SUMO1 modification stabilizes CDK6 protein and drives the cell cycle
and glioblastoma progression. Nature Communications; 5:4234. PMID: 24953629, PMCID: PMC4090607
• Pier Jr Morin et al 2015, Investigating a signature of temozolomide resistance in GBM cell lines using
metabolomics, Journal of Neuro-Oncology, Volume 125, Issue 1 pp 91-102
• Rivera B, Foulkes WD, et al. 2016, Germline and somatic FGFR1 abnormalities in dysembryoplastic
neuroepithelial tumors. Acta Neuropathol.;131(6):847-63. doi: 10.1007/s00401-016-1549-x. Epub.
• J Uniacke et al 2018, Hypoxia activates cadherin-22 synthesis via eIF4E2 to drivecancer cell migration,
invasion and adhesion O Oncogene. 2018 Feb 1;37(5):651-662. doi:0.1038/onc.2017.372.
• Phedias Diamandis et al 2019. Defining Protein Pattern Differences Among Molecular Subtypes of Diffuse
Gliomas Using Mass Spectrometry. Mol Cell Proteomics. 2019 Oct;18(10):2029-2043.
• Stephen Ponnampalam at al.2019. Determination of genetic aberrations and novel transcripts involved in the
pathogenesis of oligodendroglioma using array comparative genomic hybridization and next generation
sequencing. Oncol Lett. 2019 Feb;17(2):1675-1687. doi: 10.3892/ol.2018.9811
• Anja Kafka et al 2019. Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their
association to TCF1 and LEF1 upregulation J Cell Mol Med. 2019 Jan; 23(1): 641–655
Detailed Summary of BTTB
Operations
• Data for 2000 to 2019– Per annum
– Medians for the decade (red box)
– Trend lines
• Summaries for:– Tissues collected and donated to researchers
– Multiplier effect
– Costs of running the bank:• Overall
• Per case
• Per vial (main currency of operation)
• Per Research Group
• The BTTB has a long and successful record of providing
well-preserved, high quality brain tumour tissues to
researchers in many countries
• The operation of the BTTB is unique for its quality control
procedures and its ‘impartial’ principles of operation
• The BTTB represents one of the research arms of the BTFC
through which multiple researchers are supported ‘in kind’
• The availability of batched samples of tumours of a given
type substantially shortens the ‘bench-to-publication’ interval
• The BTTB ensures that tissues from one patient are used
for multiple research projects