Abstract
Introduction
Participants
Nine unique bioresource facilities near Tokyo participated in a voluntary study group meeting. Information on each biobank in this network follows.
Current status
This attempt to establish a biobank network is in its infancy as the activities of each biobank are introduced to the group. To solidify this network, the nine facilities made a joint presentation of their activities at the ISBER 2012 meeting in Vancouver 18 . The group plans to meet regularly and strengthen their ties.
Future plan
Our plan is to evaluate various quality assessment methods relevant for a variety of samples, and then provide the methods and references to the participating facilities and to newcomers to the bioresource research community. Eventually, we hope to set up a physical central site to provide timely assistance regarding biobank operations and governance.
Fumio Nomura, MD, PhD. E-mail:
Kazuyuki Matsushita, MD, PhD. E-mail:
Department of Molecular Diagnosis (F8), Chiba University Graduate School of Medicine, Chiba City, Inohana 1-8-1, Chiba 260-8670, Japan
URL: http://www.ho.chiba-u.ac.jp/en/contents/profile.html
1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
Tel: +81-43-226-2167, Fax: +81-43-226-2169
Hisahiro Matsubara, MD, PhD. E-mail:
Department of Frontier Surgery (M9), Chiba University Graduate School of Medicine, Chiba City, Inohana 1-8-1, Chiba 260-8670, Japan
Tel: +81-43-226-2109, Fax: +81-43-226-2113
URL: http://www.academic-surgery.jp/
Institution core budget: 0% Public targeted donation/foundation: 0% Grants: 100% User fees: 0%
Overall response to consent: Written informed consent was obtained from each patient 100% of the time prior to surgery Total individual cases held: Patients with esophageal cancer, approximately 120 cases; colon cancer, approximately 120 cases; stomach cancer, approximately 180 cases. Percent of cases associated with fresh-frozen tumor biospecimens: 80% Percent of cases associated with fresh-frozen tumor and blood biospecimens: 60%
Biomarker candidates discovered by proteomic studies of biospecimens in our biorepositories during the past 5 years: 10 Publications related to clinical features of gastrointestinal and hepatobiliary malignancy based on our biobank in the past year: 10
Whole blood samples are withdrawn into silica coated plastic venous blood collection tubes (serum: SIM-L1008S; plasma- SPM-K0707E2NA EDTA-2Na with separating agents, mixture of polyolefin hydrocarbon oligomer and silicon dioxide, KYOKUTO Co., Tokyo Japan). The tubes sit for 10 minutes at room temperature, are centrifuged at 1600g for 10 minutes (KUBOTA 5800, KUBOTA, Tokyo, Japan) 1 , and the serum samples are aliquoted mannually into 4x1.5mL slim tubes (MS-4702X) (SUMITOMO BAKELITE, CO., Ltd, Tokyo, Japan) at room temperature (20°C) and then stored at −80°C until use.
Between March 1, 2011 and June 30, 2012, peripheral venous blood samples were collected from 1,600 admitted patients using the standard procedures described above. The tumor samples were obtained from tumor epithelium immediately after surgical excision, and corresponding non-tumor epithelial samples were taken 5–10 cm away from the tumor, surgically excised at Chiba University Hospital. All excised tissues were immediately placed in liquid nitrogen and stored at −80°C until analysis.
We have paid particular attention to the effect of time intervals between venipuncture and serum preparation for serum peptidome analyses by MALDI-TOF/MS. 1 Cancer tissues and serum samples were subjected to gel-free and gel-based comprehensive proteome analyses to search for novel biomarkers and therapeutic targets. Furthermore, the establishment of electronic medical records (EMR) or medical care/electronic health records (EHR) was performed to link clinical information to each sample for clinical research. Standardized biobanking of specimens obtained from patients with gastrointestinal and hepatobiliary cancers has allowed us to increase our clinical research, as reported elsewhere.1–4
1) Funds are limited. At present, we rely on grants to particular investigators from the Japanese government. We have been requesting financial support from Chiba University Hospital on a regular basis. 2) Not all the medical staff understand the significance and importance of hospital-based biobanking. 3) We are looking at whether to use general or specific informed consent. In other words, samples to meet the investigators' specific requirements vs. samples of potential interest for future use. 4) Linking the clinical data associated with each sample to the repository system. 5) Establishing a network in which multiple tumor banks can share a common database to make collective contributions to meet investigators' requests.
Yasuo Takano, MD, PhD, Director of KCC Research Institute
Tel: +81-45-391-5761 (ext 5105)
E-mail:
Yohei Miyagi, MD, PhD, KCC Research Institute
Tel: +81-45-391-5761 (ext 5123)
E-mail:
URL: http://kcch.kanagawa-pho.jp/kikou/index.html
Institution core budget: 97% Public targeted donation/foundation: 0% Grants: 2% User fees: <1%
Overall response to consent: 98% Yes (with permission for genome analysis: 85%) Total individual cases held: 2830 frozen tissues (FFPE tissues from 581 patients, and serums/genome DNAs from 2582 patients) Cases associated with fresh-frozen tumor biospecimens: Distributed samples were 1856 frozen tissues, 581 FFPE tissues, 1020 genome DNAs and 1724 serums as of January 2012
Approximate number of studies supported last year: 9 Approximate number of cases released last year: 345 frozen tissues, FFPE sections from 205 patients, 521 serum Publications in past year (based on biobank and users): 3
The tumor tissue center is collecting tumor-related samples including frozen tumor tissues, formalin-fixed and paraffin-embedded (FFPE) tumor tissues, serum from the patients before treatment, and genome DNAs of peripheral white blood cells. Corresponding normal tissues are also collected if possible. Clinical information is annotated to each sample as precisely as possible. We are evaluating the quality of tumor samples by two indices: the RNA Integrity Number (RIN) of extracted total RNAs from randomly chosen frozen tissues examined with the 2100 Bioanalizer (Agilent Technologies, Inc., Santa Clara, CA); and histopathological examination of parts of all frozen tissues prepared in the Optimal Cutting Temperature (OTC) compound and evaluation of the contents of tumor cells.
Almost 6 years have passed since the establishment of the KCIRA Tumor Tissue Center, and two major problems appeared. One is due to the economic depression of the prefecture and the other is due to the progress of cancer research technologies and demand for raising the quality of specimens. At present, almost all the working expenses are paid by KCC, and the income of the tumor tissue center is almost negligible. Under this situation, it is difficult to increase the working expenses, and therefore difficult to increase the number of personnel. We need at least one more laboratory technologist and two more research nurses to raise the quality of samples and annotated clinical information, and to take informed consents from the patients.
At present, we keep excised organs in a refrigerator for one to two hours before sampling. Although this method maintains RIN between 6 and 8, many parameters may have changed from their original state, not only in the amount and profile of mRNAs and proteins expressed, but also in the modifications of nucleic acids and proteins. This may also influence the results from upcoming technologies. To establish a tumor tissue center with a higher quality of sample, annotated clinical information, and process informed consent, a stable increase in working expenses, such as national funding, is needed. Establishment of tumor tissue banks funded by the national budget at several cancer centers could increase the numbers of samples collected under the same quality control procedures and could promote more cancer research.
phone. +81 45 787 2733
Grants in aid from the Ministry of Education, Culture, Sports, Science and Technology
Institution core budget: 2.5% Public targeted donation/foundation: 5% Grants: 92.5% User fees: None
Overall response to consent: Yes 52%, No and Unknown 48% Total individual cases held: 1202 Cases associated with fresh-frozen tumor biospecimens: 1179
Approximate number of studies supported last year: 3 projects Approximate number of cases released last year: 106 cases Publications in past year (based on biobank and users): 2 publications
Using appropriate informed consent, the biobank is collecting human samples from healthy volunteers and the patients of our university hospital. The samples are mainly human tissues obtained at surgical operation, most of which are from cancer patients. Human tissues resected at surgery must be evaluated by the pathologists to determine future clinical management, especially in cancer patients. Thus, sampling from human tissues must be conducted carefully so as to not disturb the pathological examination. Specimens for the biobank must be freshly collected before the pathological examination. The samples are cut from the resected tissue by board eligible pathologists who engage in the pathological examination in our University Hospital. The pathologists determine the suitable sampling method for the biobank. We consider this the most important step for appropriate sampling for further research.
We have many issues to resolve and overcome for the promotion of the biobank. We do not have constant financial support. The biobank has been supported by a seven year grant from the government. The most urgent issue is how to obtain constant financial support. Another is the promotion of use of the biobanked samples. Currently, most clinical departments in our medical school store their own human tissue samples in addition to the biobank's sample collection. Thus, they use their own samples for research instead of the biobank samples. Further understanding of what the biobank has to offer may resolve this problem and could provide assurance about the integrity of the tissue samples to be used in research.
Takehiko Kamijo:
Akira Nakagawara:
Phone: +81-43-264-5431
URL: http://www.chiba-cc.jp/inst/eng/intro.html
Institution core budget: 80% Public targeted donation/foundation: 5% Grants: 15% User fees: 0%
Overall response to consent: nearly 99% Yes Total individual cases held: 8,800 adult and 2,800 pediatric samples from cancer patients (the latter has been known as one of the world's major neuroblastoma tissue banks)
Approximate number of studies supported last year: 4 adult cancers; 20 pediatric cancers Publications in past year (based on biobank and users): Since the biobank's inception: more than 240
DNAs and RNAs are routinely prepared from frozen tissues, and the quality is subsequently checked. These materials, which are securely stored in constantly- monitored freezers, have been used for state-of-the-art molecular diagnosis to determine therapeutic strategies and for basic and translational research projects upon the ethical committee's approval. The amount of sample to be used for research is separately qualified by a CCC Biobank committee.
Since establishment of the CCC Biobank in 1996, more than 240 scientific articles and reviews about pediatric cancers have been published, especially reports of neuroblastoma, the second most common pediatric solid malignant tumor derived from the sympathetic nervous system. Several retrospective studies have revealed that molecular signatures are strongly correlated with patient prognoses which has led to the construction of new risk stratification systems.5–9 Of note, anaplastic lymphoma kinase (ALK) is mutated in 6–9% of sporadic cases, and is either amplified or constitutively activated through mutations mainly within the kinase domain, promoting the possibility of new therapeutic strategies using ALK inhibitors. Additional candidates for outcome prediction such as the methylation phenotype of tumor DNA and expression profiles of non-coding RNA have also been proposed. 10 Such a variety of information will help us understand the heterogeneity of neuroblastoma biology, and further, the combined use of the signatures will be beneficial in predicting prognosis with high accuracy, as well as choosing a suitable therapy for the individual patient.
URL: http://www.s.hosp.tsukuba.ac.jp/thdc/ (available only in Japanese)
Tel: +81 29 853 3715
E-mail:
Institution core budget: 90% Grants: 10%
Overall response to consent: 100% Yes Total individual cases held: 550 (321 lung cancers; 117 colon cancers; 89 liver cancers; 9 pancreatic cancers; and 15 breast cancers) Cases associated with fresh-frozen tumor biospecimens: 100%
We manage more than 150 items of patient clinical information, including patient history, family history, and medication history. Medical technologists and research assistants perform banking of the specimens. Surgical specimens are divided into small fractions and immediately put into vials. All specimens are stored in the ultra-low freezer within 30 minutes after receipt. In THB, a research coordinator works with the doctor to obtain informed consent. We have our own consent form which is designed to be flexible in case of revision of the ethical guidelines.
To improve the administrative system in THB, we organized three internal committees (steering committee, research review board, and ethical review board) and one external evaluation committee. The steering committee consists of 12 members affiliated with the University of Tsukuba, and important decisions regarding THB are taken by this committee. The research review board and the ethical review board review research plan applications. These committees consist of experts, such as scientists, biologists, clinicians, and ethicists from various fields. The external evaluation committee consists of 4 members (legal expert, medical doctor, pharmacist, and scientist) which give advice to THB.
The system that provides samples is currently not working because of an insufficient number of samples. In the future, we would like to collect many types of specimens from other hospitals in order to fulfill the various requests of researchers. As a first step, we have established the facilities and infrastructure required for operation. Next, we plan to establish practical collaborations with other hospitals in the surrounding area. The University of Tsukuba Hospital, to which THB belongs, has already built a cooperative relationship with the local hospital for pathological diagnosis.
URL: http://www1.tmghig.jp/biobank/index.html (in Japanese)
Tel: +81-3-3964-1141 ext. 2285
E-mail:
Contacts: Dr. Tomio Arai, Bioresource Center for Geriatric Research (BRCGR), TMGH
Institution core budget: 90% Public targeted donation/foundation: 0% Grants: 5% User fees: 5%
Overall response to consent (Yes/No/Unknown %): 90%/10%/0%
41 cases (30–35 tissues in each case) Cases associated with fresh-frozen tissues: 100% Cases associated with fresh-frozen tissues and serum samples: 80%
Approximate number of studies supported last year: 0 Approximate number of cases released last year: 0 Publications in past year (based on biobank and users): 0
The bereaved family is asked to participate in the tissue bank project prior to autopsy. We take 2 cm-sized cubes of tissue samples from 30 to 35 various organs at autopsy, cut into 5 mm-sized cubes and stored in −80°C freezers. The sampled organs include left ventricle and left auricle of heart, ascending aorta, inferior vena cava, trachea, larynx, peripheral lung, esophagus, submandibular gland, liver, gallbladder, pancreas, renal cortex and medulla, ureter, prostate, uterine cervix and body, testis or ovary, female breast, pituitary gland, thyroid, parathyroid, adrenal gland, bone marrow, lymph node, spleen, skin, mesenteric and subcutaneous fat, brachial nerve, quadriceps muscle, diaphragm, lumbar vertebra, costal cartilage, and intervertebral disc. These tissues are distributed essentially free of charge to the researchers after review by a research committee and approval by an ethical committee. The characteristic feature of this tissue bank is normal tissue of various organs.
• Ensuring continued financial support for the biobank; • Implementing a public relations campaign; • Ensuring quality control of the samples; and • Setting up national and international networks.
URL: http://www.tmghig.jp/pathology-d/index.html (in Japanese)
Tel: +81-3-3964-1141 ext. 2285
E-mail:
Contact: Dr. Tomio Arai, Bioresource Center for Geriatric Research (BRCGR), TMGH
Institution core budget: 90% Public targeted donation/foundation: 0% Grants: 5% User fees: 0%
Overall response to consent (Yes/No/Unknown %): 100% of autopsy cases
Cases associated with fresh-frozen tissues: 100% Cases associated with fresh-frozen tissues and serum samples: 80%
Approximate number of studies supported last year: 19 Approximate number of cases released last year: 2,000 Publications in past year (based on biobank and users): 11
The Collaborating Project has started to promote the use of all autopsy materials and information derived from the TMGH-Autopsy Resource (TMGH-AR) since 2009. No medicolegal autopsy is included. The average age at death of the patients is 80 years and male to female ratio is approximately 1:2. Since 1972, all clinical and pathological information from more than 7,600 cases has been stored and kept updated in a database called ANATOMY. 11 We have also developed a geriatric autopsy database for molecular epidemiological studies on more than 2,500 cases, which contains histories of smoking and drinking, clinical diagnosis including 26 geriatric diseases, serum lipid data, 750 pathological findings, 42 major pathological diagnosis, atherosclerotic degrees of 10 major arteries, and emphysematous degrees. 12 We have started storing serum taken before death since 1995, with more than 2,000 serum samples currently available. Tissues from kidney, liver, heart and lung (or esophagus) have been kept frozen in deep freezers in all cases since 1995, and DNA has been extracted from unfixed renal tissue (2,500 cases) or from paraffin sections (5,200 cases).
• Ensuring continued financial support for the biobank; • Implementing a public relations campaign; • Ensuring quality control of the samples; and • Setting up national and international networks.
URL: http://raredis.nibio.go.jp/
Tel: +81 72 641 9019
E-mail:
Contacts: Dr. Ichiro Takahashi (Director), Dr. Ryuichi Sakate, Dr. Tohru Masui
April, 2009
2009–present
Human biospecimen of rare diseases
Basic/Translational
Institution core budget
Institution core budget: 90% Public targeted donation/foundation: 0% Grants: 10% User fees: <1%
Overall response to consent (Yes/No/Unknown %): N/A (consents are handled by collaborating institutions) Total individual cases held: 205 for 39 diseases (Genomic DNA from 111 patients, plasma/serum from 158 patients, and cells from 56 patients as of June 2012 - some of these are not ready to be released.)
Approximate # of studies supported last year: N/A (just started to release this year) Approximate # of cases released last year: N/A (just started to release this year) Publications in past year (based on biobank and users): 4
The Rare Disease Bank was established in National Institute of Biomedical Innovation (NIBIO) by the Ministry of Health, Labour, and Welfare, Japan (MHLW) in 2009. The objective of the bank is to centralize and impartially distribute rare disease specimens with quality control in order to promote research on rare diseases. Specimens are collected in collaboration with the MHLW's research projects to overcome intractable diseases (130 projects). An institutional review board (IRB) was instituted at NIBIO to exclusively serve the bank reviews prior to collection/distribution of specimens.
The bank started distributing specimens to researchers in October 2011. The bank can currently distribute genomic DNA, serum and plasma from patients with 14 diseases (e.g., HTLV-1-associated myelopathy 13 , Kennedy disease 14 , Primary aldosteronism 15 ). Information regarding distribution of specimens is available from the Rare Disease Bank website (http://raredis.nibio.go.jp/, currently in Japanese only). In order to obtain detailed information on the specimens and apply for distribution, users must be registered.
The Rare Disease Bank is managed based on “Ethical Guidelines Regarding Human Genome and Genetic Analysis Research” (Ministry of Education, Culture, Sports, Science and Technology, MHLW, and Ministry of Economy, Trade and Industry). Under the guidelines, human specimens should be distributed from biobanks in an unlinked and anonymizedmanner. In line with this, neither the bank nor the specimen-collection group should handle inquiries from researchers regarding the specimens after distribution. However, it is sometimes important to distribute further clinical information on specimens to researchers, while conveying their inquiries to clinical doctors.
Division of Clinical Laboratories
National Cancer Center Hospital (NCCH)
5-1-1, Tsukji, Chuo-ku, Tokyo, 104-0045 JAPAN
Tel: +81-3-3542-2511 Fax: +81-3-5856-7570
Koh Furuta
E-mail:
Tel: +81-3-3542-2511
Fax: +81-3-5856-7570
October, 2002
January 1st, 2006 to present. Samples collected during October 2002 to December 2005 were discarded. Storage duration is for five years.
Basic research
Mainly clinical, partially translational research
Hospital budget and grant from government (the Ministry of Health and Labour).
Institution core budget: 40% Public targeted donation/foundation: 0% Grants: 60% User fees: 0%
Overall response to consent (Yes/No/Unknown %): 90% Yes/less than 1% No/9% Unkown
Approximate number of studies supported last year: 14. Approximate number of cases released last year: 3084 samples. Publications in past year (based on biobank and users): 5.
Two technicians and one doctor are the working force in this NCCH-Biobank. Stored samples are mainly blood, such as plasma and serum. In addition, buffycoat, DNA, and RNA are collected, although in small numbers. Blood samples are stored at −20°C using regular cryotubes. Samples collected before September 2011 are stored in 5 ml cryotubes. Samples collected after that time are stored in 1 ml 2D barcoded cryotubes. The NCCH provides a broad opt-in consent format to the patients for the purpose of utilization of samples for other than their own medical necessities. Institutional Review Board approval is mandatory for use of the samples. Currently in-hospital doctors and researchers, including outside personnel under collaboration with in-hospital personnel, can apply for sample utilization.