Development of a National Canine Cancer Biospecimen Repository:

The Canine Comparative Oncology and Genomics Consortium

Matthew Breen, PhD; North Carolina State University

 

I. CCOGC Background

In June of 2004, an informal collaboration of veterinary and medical oncologists, pathologists, surgeons, geneticists, and molecular and cellular biologists emerged at a meeting hosted by the Broad Institute, in Boston, MA. These investigators shared a common interest, the comparative study of canine and human genomics and cancer. With the imminent availability of a high quality canine genome assembly, they sought to leverage opportunities that would result from a better defined understanding of the genetics and biology of cancers in companion animals, to provide a forum for discussion and sharing of resources and reagents, and to guide the development of novel technologies that would allow the study and use of appropriate canine cancers in the global study of cancer biology and therapy. Over the ensuing months this collaboration named itself the Canine Comparative Oncology and Genomics Consortium (CCOGC) and began drafting an agenda and list of priorities. In 2007 the CCOGC incorporated as a Not-For-Profit and obtained 501(c)3 status. The goals of the CCOGC are to facilitate strategic partnerships and collaborations across a diversity of disciplines, focused on the problem of cancer in dogs. Early priorities of the CCOGC include advocacy for the field of Comparative Oncology, the development of a mechanism to share reagents and resources in the community, and the development of a biospecimen repository.

 

II. Biospecimen Repository

CCOGC collaborators determined that an essential resource needed in the field was the development of well-described repository of tissues (tumor and normal) from tumor bearing dogs. To be optimally useful this biospecimen repository would be:

. Focused on specific cancers of interest to the field . Centrally housed with multiple contributors

. Populated with prospectively collected tissues and fluids . Annotated with robust parallel clinical data-base

. Managed through a web-enabled entry and retrieval port

. Publicly accessible based on scientific merit or requesting individuals

 

Based on this the repository has begun with a goal of collecting tissues and fluids from 3,000 dogs with specific cancer types over a three-year period. The specific cancers will represent those that are not only major problems in the dog population, but which are also have comparative value in human cancer investigation. Universal and cancer specific standard operative procedures have been defined for the collections. The bank is housed centrally within a contract biospecimen repository in Frederick Maryland with contributors including qualified schools of veterinary medicine in the United States. A caBIG (https://cabig.nci.nih.gov) complaint web-based relational data-base has been implemented to track sample shipment, to describe sample characteristics and clinical annotation of patients, and to allow review of bank assets.

 

III. Biospecimen Repository Operating Model and Funding

The operating model developed for the CCOGC Biospecimen Repository was based on a population phase that would require $2.2 million of start up funds, sufficient for the collection of 3000 patient samples at 10 institutional collection centers in the United States. Upon population, requests for use of tissues I would be reviewed and granted to individuals and institutions based on scientific review. In an effort to repopulate the repository, the CCOGC has designed a perpetual support model for the bank. Using a

 

 

 

 

 

 

 

 

 

 

 

 

nominal fee cost structure, differentially applied to not-for-profit (NFP) and for profit requests the CCOGC Biospecimen Repository will generate income sufficient to maintain the tissue resource that will be depleted through sample use and sustain the administrative activities of the CCOGC (Figure 1). A final component of the operating model would be to use the repository collection infrastructure to service contract requests for prospective collection of samples (Figure 2). Agreements have been drafted to define ownership of material and intellectual property emerging from requests made to the 3000 patient bank and for prospective collection contracts.

 

 

 

 

 

 

 

 

 

In 2006, the CCOGC entered into a strategic partnership with Morris Animal Foundation (MAF) and the AKC Canine Health Foundation (CHF) to seek the funding needed to establish the tissue bank. This partnership resulted in the boards of the CHF and MAF approving funding to the CCOGC of $250,000 each and a further commitment to assist in seeking the remaining $1,700,000. With $500,000 in initial funding, the CCOGC released a request for proposals from US institutions that wished to be considered as CCOGC collection sites. In the summer of 2007, Pfizer Animal Health provided a lead gift in the amount of $1,100,000 through a working relationship with the MAF. In recognition of the importance of this gift, the formal name was changed to "Pfizer-CCOGC Biospecimen Repository".

 

The Pfizer-CCOGC Biospecimen Repository has received support from the intramural National Cancer Institute to establish and maintain a physical bank in Frederick Maryland and to have this bank linked to a web-enabled interface for access to tissues. The physical bank is managed by Fisher Bioservices and is part of the NCI Frederick Central Repository Services. The facility is over 33,000 sq ft, has 24-hour temperature monitoring, four 250KW generators, and back-up generators (Figure 3) . The bank consists of -80C freezers, chemical storage for formalin fixed and paraffin embedded tissues, bar coding hard and soft ware and web enabled sample management system. The bioinformatics platform for the repository includes a relational database that will connect clinical information on samples entered to the study with a front and back end retrieval system. Biological data derived from samples in the Biospecimen Repository are uploaded into the bioinformatics database and become part of the progressive value of the Repository. It is expected that the value of this biological data will exceed the physical value of tissues over time.

 

Figure 3. Pfizer-CCOGC Biospecimen

Repository housed at NCI Frederick Central Repository.

 

The biospecimen repository houses tumor tissue, normal tissues, serum, plasma, peripheral blood mononuclear cell preparations, genomic DNA, RNA and urine samples. Each of the 3000 cases will have tumor and normal tissue collected and processed in both ethanol and two frozen formats (both flash frozen and OCT embedded). Whole blood is collected and divided between DNA and RNA PAXgene^TM collection tubes. Approximately 5 to 6 ml of serum and plasma will be processed in addition to 3ml of urine. The repository follows many parts of the organization and structure of the proposed National Biospecimen Network Blueprint]. Standard operating procedures of tissue/sample collection have been established and are subject to annual review.

 

Standard operating practices (SOP) for collection of a diverse set of disease and normal tissues from each canine patient have been developed as part of the Biospecimen Repository SOP. When developing the SOP, the CCOGC Bank Committee referenced the National Biospecmien Network Blueprint!, the American College of Surgeons Oncology Group SOp2 and the IUPUV Clarian SOp3. The SOP describes the procedures for tissue and sample collection to be used at defined CCOGC Collection Sites. The procedures described in the SOP cover universal aspects of sample acquisition, preparation, and shipping to the CCOGC Biospecimen Repository. The Universal SOP focuses on the collection of whole blood, serum, plasma and urine. Each histology of interest has a separate SOP that is an appendix to the Universal SOP. The appendices outline the collection of nonnal and tumor tissue relevant to each histology. All prospective collections will be added as an appendix to the SOP.

 

Sample quality and assurance will be reviewed and recorded contemporaneous with sample collections.

 

Pfizer CCOGC Biospecimen Repository Tissues

It was decided that the specific cancers to be selected should represent those that were not only major problems in the dog population, but which also have significant comparative value in human cancer investigation. Accordingly cancer specific goals included the collection of 600 samples each from dogs with lymphoma, osteosarcoma and melanoma. Samples collected from each patient will include tumor, normal tissue, blood, and urine. An additional 1,200 samples would represent four other histologies (300 each), selected in consultation with the broader community and sponsoring agencies. These additional cancer histologies will be selected during 2007.

 

Comparative Pathology Review

For each cancer histology identified for collection a web-based and digital pathology review will be organized. The goal of this pathology review will be to validate the diagnosis of submitted tissues and to provide a forum for comparative assessment of canine and human cancers. The pathology reviews are being organized by Mark Simpson, DVM, PhD, ACVP. These reviews will involve highly regarded veterinary and human pathologists and will yield position papers on the pathological description and comparative description of cancers by histology.

 

Access to Tissues

Once the repository has been populated with the initial 3000 samples, access will be granted to the bank. Rules for governing the access to the CCOGC Biospecimen Repository have been established. The CCOGC will solicit proposals annually. The Biospecimen Repository Committee (BRC) will perform review of these proposals and will consider several factors including the attainability of the proposed objectives, scientific merit, adequacy of experimental design, and the ability to support further definitive studies. Principle investigators of approved projects will provide updates to the BRC every six months to ensure that satisfactory progress is being made.

 

Progress

Collection Site Selection. The Pfizer CCOGC Biospecimen Repository has initiated collection of tissues at three institutions (Colorado State University, Ohio State University and the University of Wisconsin-Madison). Institutional sites'were selected by competitive review of applications responding to a CCOGC RFP. Sites were selected based on case-load, experience with sample collection, personnel and physical infrastructure, and institutional commitment to the banking effort. A second RFP has been recently distributed to all US Colleges of Veterinary Medicine that seek to identify up to seven additional collection sites that will work towards the initial 3000 patient collection goals for the repository.

 

Sample accrual. As of August 1st, active collection sites have collected tissues from 37 cases. This rate of patient accrual has exceeded our goal of collecting 25 patients in the first six months of collection.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 4. CCOGC samples collected by month 3 (August 2007). A total of 37 cases have been collected.

 

Resources and References

1. National Biospecimen Network Blueprint. Stem, Susan et al. 2003

2. American College of Surgeons Oncology Group. Standard Operating Procedure. SOP ill: SpecBank. 2003

3. IUPUI/Clarian SOP for Collection, Storage And/or Use of Biological Specimens

 

Biographical Profile

 

Dr. Matthew Breen completed his PhD in cytogenetics in 1990 and then spent two years as a Post Doc in Molecular Genetics at the UK Medical Research Council's Human Genetics Unit in Edinburgh, Scotland, where he was responsible for developing novel ways to map genes to chromosomes as part of the Human Genome Project. Dr. Breen then spent four years working for the research arm of the Australian Thoroughbred industry, returning to the UK in 1996 where his laboratory .developed molecular cytogenetics reagents, resources and techniques for application to canine genome mapping, comparative cytogenetics and cancer studies. In 2002 Dr. Breen relocated his laboratory to North Carolina State University's College of Veterinary Medicine, where he is Professor of Genomics and also a member of the Center for Comparative Medicine and Translational Research (CCMTR). He also serves as Director of the CCMTR's Clinical Genomics Resources Laboratory.

 

Canine Comparative Oncology and Genomics Consortium – conference notes

 

Update on the CCOGC:

            $$$ and expertise

            Samples samples samples (like in real estate: location location location)

Need to consolidate sample repository so it is easier to begin work once it is funded.

It is a community of investigators and institutions interested in the study of cancer in companion animals.

 

CCOGC will facilitate strategic partnerships and collaborations across a diversity of disciplines, focused on the problem of cancer.

 

CCOGC was incorporated in November 2006 and is also a registered not for profit 501C3 organization.

 

Tissue samples will include:

            Osteo

            Lymphoma

            Melanoma

Other cancers seen in dogs will be selected by votes from the CCGOC, CHF, Morris Animal Foundation and Pfizer.

 

CCOGC partnered with Morris Animal Foundation, AKC CHF and Pfizer to fund this project.

 

Who will get these samples once collected?

            CHF, MAF and other grant applicants?

            Pharma-Biotech

            Academia

*will need to prove that samples will be used samples wisely and that funding is in place to perform research fully

 

By January 2008 6-8 collection sites will be opening and functioning.  Right now open at:  Ohio State University (Dr Laura Rush), Colorado State University (Dr Sue Lana), University of Wisconsin – Madison (Dr David Vail)

 

Samples are stored at the Wedgewood Repository in Maryland, where human samples are stored.  They are secure and safe.

 

Repository is ahead of projected sample collection projections. 

 

Repository value –

            Open access

            Shared/common resource

            Progressive value resulting from common tissue evaluation

            Sustainable resource

            Leveraged against existing national infrastructure

 

The CCOGC will enhance the outcome of investigator initiated research in the field of canine oncology.

 

Contact: ccogcadmin@gmail.com