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

How are the Tumour Samples Processed and

Stored?

(All tumours)

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

2010-2019

2010-2019

Number of Shipments and Research Groups

Receiving Tissues: 2010-2019

• 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