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BioBanking at The Princess Margaret
Introduction
BioBank 'Consumers'
BioBank Donors
The Biotechnology Side of BioBanking
The IT Side of BioBanking
BioBank Challenges: What does the UHN BioBank Need to Catapult Cancer Research?
Biographies of the BioBank Leaders
Multimedia
Further Reading
Introduction
The work taking place in a world-class research hospital such as Princess
Margaret Hospital (PMH) tends to fall largely into three areas:
- Clinical care of patients
- Clinical research involving patients (e.g., testing new drugs and treatments)
- Basic science research
The goal for every doctor, nurse and researcher is to provide more effective care and treatment for cancer patients. The challenge for the leaders of the
hospital is leveraging
the work in each area to make greater progress overall.
The term ‘translational research’ is also heard often and it refers to research that can only take place in a setting like Princess Margaret, with a large patient population and a substantial research operation. It is research that stretches from the laboratory bench to the bedside. At PMH, many patients have advanced or very aggressive types of cancer, and they come to this hospital because the best treatment is available. Because of their
situation, they are often very anxious to assist with cancer research in whatever ways they can. One area where patients can help is in building up the BioBank.
A biobank, simply, is a place that stores any biological specimens taken from patients or healthy individuals. This could be blood or tissue from a tumour removed, or it could be spinal fluid, urine, or nail clippings. It is important to note that an optimal biobank contains tissue specimens from healthy individuals as well as patients suffering from the disease or condition being studied, as scientific tests need a ‘control’ group.
In the world of cancer research, the term ‘tumour bank’ has been used for some time. However, ‘biobank’ is now preferred, as the banks typically collect and store more than tumour tissue. Because PMH is part of the University Health Network (UHN), our biobank contains blood and tissue samples from cancer patients as well as people who do not have cancer.
Dr. Patricia Shaw heads up the UHN BioBank. She is a pathologist and also leads a team of researchers in the area of ovarian cancer. A link to a video interview with Dr. Shaw is given below.
BioBank
UHN conducts over 23,000 operations annually from oncology-related procedures to cardiac to orthopedic. This presents a huge opportunity for building a specimen-rich BioBank. UHN also operates in Toronto, one of the most ethnically diverse cities in the world.
The majority of the surgical patients treated at Princess Margaret are asked if they would be willing to donate blood and other tissues to the BioBank. It must be done through a formal ‘informed consent’ procedure and according to privacy legislation. Our statistics indicate that, when asked, the large majority of patients agree to the request especially when they are confident that their ‘gift’ will help in the work of developing better treatments.
Building a successful BioBank requires a multi-disciplinary team that brings together talents in both biotechnology and information technology. Connecting the specimens with patient data (including family health history and clinical treatment-related data) accurately and efficiently, and then ensuring that it is ‘de-identified’ when researchers access it is equally important to collecting the blood and tissue samples. ‘De-identification’ is an extremely important step and ensures patient privacy and confidentiality. It means that any information that could personally identify a tissue or specimen (e.g., name, address, phone number, health card number) is ‘locked’ and made inaccessible to the research staff.
This document discusses both components of a BioBank—physical specimens and related patient/treatment data—and will highlight the direction that Princess Margaret Hospital is taking in growing and expanding its bank.
Biotechnology |
Information Technology |
- Collection of blood and tissue specimens
- Quality control (ensuring the specimens are high quality)
- Processing the specimens (weighing, measuring, and grading/classifying)
- Storage of specimens in secure areas with back-up power systems
- Digital imaging
- Preparing samples for researchers
- aliquoting (dividing sample into many small pieces)
- tissue microarrays, RNA
- laser capture microdissection
- Meeting with researchers who need tissue to determine how best to meet their needs now and in the future
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- Recording the patients’ consent to bank their blood and tissue in a secure, legal and approved manner
- A computer information system that:
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records all necessary details regarding the blood and tissue samples at the time of collection |
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identifies each specimen uniquely, and allows the physical specimen to be labeled through a bar code or something similar |
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links to the patient database so that family history and treatment history can be accessed |
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ensures patient data is secure and de-identified when researchers access it |
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allows researchers to query or receive reports on available specimens |
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allows specific specimens to be located and destroyed should a patient change their mind about having their blood or tissue banked |
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BioBank 'Consumers'
Before exploring these areas in greater depth, let’s look at how some of the researchers at PMH are making use of the BioBank.
Research Study: Early detection of ovarian cancer
Dr. Jim Greenaway joined Dr. Pat Shaw’s research team in 2008 to help identify biomarkers or indicators of early ovarian cancer. We know that the earlier a cancer is detected, the easier it is to treat, so the focus of many researchers at The Princess Margaret is to find these ‘early signs’ of cancer. The PSA test, now part of most men’s annual physical, is a good example of a useful tool for a doctor looking for early indicators of prostate cancer. Ovarian cancer is very difficult to detect until it has advanced to a late stage, and Dr. Greenaway looks forward to the day when there is a blood test or a saliva test that doctors can request for ovarian cancer. His research is paving the way.
To do his research, he is testing and analyzing tissue obtained from the BioBank. The tissue is from:
- ovarian cancer patients
- ‘healthy’ patients (those with no sign of ovarian cancer), and
- women who are at high risk for the disease (e.g., those with a recognized mutation to the BRCA1 gene)
Dr. Shaw suspects that ovarian cancer may begin with mutations or cellular changes that take place within the fallopian tubes of a woman, so she has collected tissue from women who have given consent and undergone gynecological surgery at University Health Network. Without this collection, this ground-breaking research would not be possible.
Dr. Greenaway’s tissue samples are then analyzed using a fairly new technology called microarray analysis. Microarray technology allows researchers to examine and compare the expression of many genes within the cells of the different types of tissue. Disruptions or changes in gene expression are responsible for many diseases. For example, HER-2 is a gene implicated in an aggressive type of breast cancer that is usually referred to as HER-2 positive breast cancer. If Dr. Greenaway is able to pinpoint a particular gene (or two) that is highly expressed in ovarian cancer tissue, it could lead to new tests or preventative strategies, as well as new treatments for the disease.
Research Study: Searching for a ‘signature’ for breast cancer
Dr. Mona Gauthier, principal investigator with the Campbell Family Institute for Breast Cancer Research, leads a team that is doing similar work to Dr. Greenaway, but for breast cancer.
Dr. Gauthier was recruited to Princess Margaret from the University of California San Francisco where she completed her post-doctoral training. “A well-annotated tissue BioBank is a critical bridge between the clinic and the research laboratories, and the only way we, as a community, can understand disease at a molecular level,” she explains.
She and her team are also working to develop molecular tools that will help identify tumour cells that develop treatment resistance and therefore patients at increased risk of developing re-current disease.
Dr. Gauthier believes “the BioBank is the glue for these collaborative, productive and forward-thinking projects.”
In describing her needs from a BioBank, she highlighted the importance of having access to the detailed clinical (non-personal) information (e.g., family history of disease, estrogen receptor status, evidence of metastasis (for breast tumour tissue), involvement of lymph nodes).
Research Study: Ovarian cancer stem cells
Jocelyn Stewart works in the lab of Dr. Ben Neel, and as a graduate student, she is conducting research at the hospital in the isolation of cancer stem cells in ovarian cancer.
To conduct this research, she needs a regular supply of ‘live’ (i.e., not frozen) ovarian tumour tissue which she tests and analyzes, looking for ‘markers’ that identify the cancer stem cells believed to be the root of the disease. Cancer stem cells may be more resistant to current chemotherapy and other cancer treatments, so scientists are anxious to isolate these cells and understand them better in order to develop more effective cancer therapies.
In the past 18 months, the BioBank has provided her with samples from over 160 patients. This includes tissue from the primary tumour and, if possible, tissue from any metastasis (or spread) from the primary tumour.
Because of Jocelyn’s research and other research at The Princess Margaret, the surgeons treating women with ovarian cancer are consistently asking the women if they are willing to have their tumour tissue banked for research. This has provided an excellent supply of tissue for testing.
Jocelyn says there has been wonderful support for her research from the clinicians in the hospital. She noted that in meetings with ovarian cancer surgeons and care givers, it was brought to their attention that the ascites fluid that builds up in the abdomen of women with late stage ovarian cancer contains a high percentage of cancer cells that may be used in her studies. The collection of these chemotherapy naїve fluids is currently being implemented through the BioBank, and Jocelyn will have a steady supply of ascites fluid that she can also use in her research. This would not have come to light if there weren’t good communications between the clinical staff, the BioBank team and research groups.
BioBank Donors
The research just described is only possible because the majority of surgical patients being treated at The Princess Margaret said ‘yes’ when asked if they will donate tissue specimens to the UHN BioBank.
Because we now understand that cancer is a disease of the genome, patients understand that other members of their family could also be affected by cancer some day. This is a significant motivator for someone to donate to a BioBank, but most patients simply want to do something to help find better treatments and techniques for early detection so other people will be spared the anxiety and difficulties associated with many of today’s treatments.
As a patient who was treated for ovarian cancer at Princess Margaret, Jane Jankovic did a lot of research on her condition. She shares her thinking back when she was asked if she would contribute her tumour tissue to the BioBank.
As a BRCA1 patient*, my body bits may contain a piece of information about how the cancer manifests, and, therefore, what to look for, and when and where. My cancer started in my tubes, which would never have been discovered if not for scrupulous lab analysis.
Ovarian cancer is notorious for late diagnoses, and presumably that is why it has among the most pessimistic of prognoses for patients. Improved treatment, while maybe easier to manage, has not proved to have much impact on mortality rates. So it seems to me that early diagnosis is that only thing that will make any meaningful difference for women. And I was eager to be part of that exploration.
Jane Jankovic
(*BRACA1 is a gene identified as one contributing to a high risk for breast and ovarian cancer)
Treating over 1,000 patients each day in a large and culturally diverse city, PMH has the potential to build a very large and rich BioBank. Already the BioBank has over 50,000 tissue specimens banked, from over 18,000 different patients.
Andrea McManus is a mother of three daughters and a breast cancer survivor. Below are her words on why the BioBank is a priority for her.
My cancer is of a genetic origin. My mother had breast cancer twice, once when she was 41 and pre-menopausal and again when she was 71. I had bi-lateral breast cancer diagnosed at age 49, and I was pre-menopausal. I always knew I was high risk, and I would have donated to the BioBank whether or not it had been confirmed as genetic cancer. At the time I had breast cancer, my three daughters were all in their mid-teens. I want to do whatever I can do to guard their future in having to deal with breast cancer. While that is the primary and most personal reason, I also feel that I have a responsibility to do what I can to help other women in the future. Donating my tissue is such a small and easy thing to do, but a hugely important contribution to future treatments/cures.
Andrea McManus
To be successful, the BioBank must place a high priority on the development and strict adherence to procedures that are approved and well-documented. Donors must be confident that their specimen donations are not being wasted, but are put to good use, and that their personal information is always safeguarded, and not made available to the researchers who use the BioBank.
Procedures must also exist that enable a donor to remove his blood and/or tissue specimens from the BioBank should that be necessary for any reason.
The Biotechnology Side of Biobanking
How are specimens collected?
Almost all biobanks collect and store blood or blood components. Blood is easily collected in hospitals and is done routinely at PMH when patients arrive for treatment. With blood, the BioBank needs to determine which patients should be asked to donate and how often to bank a patient’s blood. For example, for a patient on a clinical trial for a new drug, the patient’s blood may need to be taken and banked after each treatment.
 Any tissue or cells removed from a patient during a surgical procedure become the medical responsibility of the pathologist as soon as it is removed from the patient. Under the guidance of the pathologist, some of this tissue will be banked for future research. Procedures have been developed that ensure the banking of tissue is given a high priority, as tissue can degrade quickly if it is not handled appropriately, and researchers depend on high quality specimens. The rest of the tissue is used for diagnosis and determining the prognostic factors by the pathologist. This information is then relayed to the treating oncologist. At no point in time is the clinical care and diagnosis compromised by the biobanking procedures.
Research being conducted at the hospital tends to drive or influence what specimens are collected. However, for a large cancer centre such as The Princess Margaret, the BioBank is collecting samples with a view to supporting research that might not yet be funded or anticipated.
Cancer researchers hope to develop simple tests for cancer that could be done using a person’s blood, saliva, or sputum. A great deal of blood is already banked at PMH, especially among patients who have been diagnosed with blood cancers like leukemia, and the goal is to expand blood banking even further. To bank saliva and sputum on a regular basis would require additional resources, including additional personnel and storage facilities.
How are specimens processed?
There are several steps required to ensure the high quality of specimens in the BioBank. First, each tissue sample must be validated to ensure that it is what the label says it is. Accurate labeling is obviously key in order for researchers to make proper use of the specimens. This step must be completed by a trained pathologist or pathology assistant, and it is referred to as Pathology Validation.
Tissue samples are weighed, measured and then classified or evaluated according to certain parameters. This information determines each specimen’s appropriateness for different types of research. All the information needs to be recorded in a way that is easily accessible to researchers using the sample. For example, some tumour tissue may be very ‘high grade’ meaning it represents an advanced stage of cancer, while other tissue may contain much less cancerous tissue. Some research, particularly research involving gene profiling, requires ‘high-grade’ tumour tissue.
Production of derivatives
Production of derivatives refers to the process of turning tissue samples into formats that will be useful to researchers. Formats include:
- Sliced and mounted on slides or used to make tissue microarrays
- Derive and store viable cells (cells are ‘immortalized’)
- Proteins, RNA or DNA are extracted from the tissue in anticipation of high throughput gene profiling experiments
How are specimens stored?
Some researchers require fresh tissue that does not get preserved or frozen. In these cases, tissue is typically inserted into vials that have been provided to the pathology department by the researcher. For tumour samples that are being preserved,
the most common format is to preserve the tissue in a fixative, most commonly formaldehyde, and then embed it in a small block of paraffin wax. From this format, thin ‘slices’ can be obtained quite easily.
Another common format is to freeze the tissue cryogenically. The tissue might also be embedded in a material that allows it to be cut easily when frozen. The samples are either stored at -86
degrees C in freezers or at -196 degrees C in liquid nitrogen. The storage units must be highly organized and compartmentalized, with each sample having a computer-tracked location.
All samples are given a unique identifier and usually a barcode for easy scanning. Each item in the BioBank will occupy a unique and computer-tracked location.
All biobanks must have plans for proper security, backup power, and backup storage in case of the failure of any storage or cooling devices.
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