(1) Bioresource Overview

Project description

The Centre de Ressources Biologiques-Tumorothèque ICO originates from the grouping of Tumor Bank of ICO created in 2002 located in Angers (FR) and biobank based at ICO Saint-Herblain (FR) created in 2003. The ICO biobanks initially shared with the University Hospital of Nantes was individualized from 1st July 2018 and became the CRB-Tumorothèque ICO. Samples are collected at both sites of the cancer center (Saint-Herblain and Angers), and the storage and delivery centralized at the Saint-Herblain site. The management of biocollection activities is carried out as part of a NF S 96 900 certification renewed in December 2018. The CRB-Tumorothèque ICO manages biological collections from multiple cancer types or collected in clinical trials in which ICO participates as a sponsor or through the physicians who are investigators. Eight biocollections entitled: breast-gynecology, genitourinary system, digestive system; nervous system; sarcomas; aerodigestive track; endocrinology; hematology are declared and registered under the reference DC-2018-3321.

The CRB-Tumorothèque is composed of three activity sectors: 1) “Tumor Tissue Bank” which collects tissue samples; 2) “biology” sector which collect biological samples and their derivatives other than tissues (e.g. blood, urine); 3) “clinical trials” sector collecting all samples related to clinical research protocols (Figure 1). The main objectives of the CRB-Tumorothèque are to ensure the traceability of all samples and associated processes to make them available to the scientific community for translational research projects.

Figure 1 

Organization of the CRB-Tumorothèque ICO and flowchart process. Similar flowchart is required by the numeric data center to get access to clinical annotations. *: http://www.ico-cancer.fr/la-recherche/centre-de-ressources-biologiques-tumorotheque/; +: validation; –: rejection.

Classification (1)

Human

Species

Human

Classification (2)

Biological samples, biological samples and associated data, data only, clinical data

Context

Spatial coverage

Description: Centre de Ressources Biologiques-Tumorothèque, Institut de Cancérologie de l’Ouest, Boulevard Jacques Monod, 44805 Saint-Herblain, cedex, France

Latitude: 47°14’16.4863”

Longitude: –1°38’15.2622”

Temporal coverage

Start from 2002 to present, no end date.

Temporal coverage for accessibility

N/A: CRB-Tumorothèque ICO has no indicated date when bioresources must be destroyed.

(2) Methods

Steps

Recruitment

Patients diagnosed and treated at ICO for an oncologic disease who gave their agreement and have signed off the informed consent are eligible for the CRB-Tumorothèque. Patients are included at all clinical Departments. Biological resources can be also collected from external clinical centers and are couriered by certified transporters to the CRB-Tumorothèque ICO within an adequate period of time according the nature of bioresources.

Collection of bioresources

Each clinical/surgical department of ICO collects biological samples in a uniform way and in a routine clinical care setting. Standard Operating Procedures have been established and validated for all laboratory methods related to the bioresources. Each process used at the CRB-Tumorothèque ICO intregrates: staff education and training, safety procedures, access to the facility, logistics, identification of equipment/device and consumables, temperature control, document control, consent procedures, sample intake, handling, storage and distribution (SOPs), services, non-conformities, audit and management review. All these information/procedures are documented in a quality management system under supervision of the quality manager.

A request form including patient identification, material collected, date and time of the collection, informed consent is joined to the resource. Biological samples without informed consent are not processed.

All biological materials sent to the CRB-Tumorothèque ICO are delivered as fast as possible to guaranty the quality of the biological samples.

Preparation/transformation of bioresources

Biological fluids and derivates, and tissue samples are processed by trained and certified staff through the biopathology department (histopathology and biology departments). Tissue specimens are validated by certified pathologists. Only surplus material is passed to the CRB-Tumorothèque ICO.

Immediately after receipt, samples are registered thanks the TumoroteK software, de-identified and processed according to the corresponding procedures. All steps of the process are documented into TumoroteK system. Tissue samples are stored as frozen or Formalin-Fixed Paraffin-Embedded (FFPE) material. Biological fluids (e.g. urines, stools) and derivates (e.g. plasma, serum, DNA, RNA) are aliquoted and stored at –80°C.

Only trained staff of the CRB-Tumorothèque ICO has access to the databases and the physical collections. In close collaboration with the numeric data center, staff has access to other databases of the ICO cancer center to retrieve clinical data, associated with the patient.

Stabilization/preservation

Tissue

  • – Formalin fixation and paraffin embedding
  • – Snap freeze tissues in isopentane and/or liquid nitrogen

Serum

  • – With or without clot activator (blood to clot in an upright position for at least 30 minutes but not longer than 1 hour before centrifugation)

Plasma

EDTA: centrifuged EDTA blood within 30 minutes

Cells

  • – Buffy coat: centrifuged EDTA/ACD blood at reception
  • – Peripheral Blood Mononuclear Cells: EDTA blood and Ficoll preparation
  • – Circulating Tumor cells [EDTA or Cell-Free DNA BCT (Strek, USA) or Cell Save tubes (Silicon Biosystem/Menarini, Italy)]

cfDNA

  • – PAXgene Blood ccfDNA tube (Quiagen, France)

Type of long-term preservation

All bioresources prepared (Formalin Fixed Paraffin Embedded, frozen and cryogenic preserved samples). Preservation in access-controlled and temperature monitored facility.

Storage temperature

Depending on the bioresource:

  • – FFPE samples at room temperature (18–25°C)
  • – Snap freeze tissues at –80°C
  • – Serum, plasma and cfDNA at –80°C
  • – Cells at –196°C (liquid nitrogen)

Shipping temperature from patient/source to preservation or research use

Room temperature (18–25°C)

Shipping temperature from storage to research use

Depending on the bioresource:

  • Room temperature: FFPE samples
  • –80°C (on dry ice) (DNA, Plasma, Serum, Cells)

Quality assurance measures

All activities are carried out according to the French National Cancer Institute (INCa) recommendations [1, 2, 3].

Samples are processed according to Standard Operating Procedures by trained and qualified staff. All process steps are recorded into the TumoroteK (TK) data manager system which automatically generates an anonymization code for each sample linked to each biocollection. The measures established for ensuring the quality of samples include:

  • – Suitability of reagents for the sample processing and use of controlled/monitored laboratory materials.
  • – Procedure of intervention in case of an electrical blackout to safeguard samples with adequate alarm systems for frozen devices.
  • – Setting up of a risk-management storage system for each sample in separate freezers.
  • – Maintenance of the database up-to-date.
  • – Quality controls: e.g. DNA/RNA quantification and integrity validated by DNA/RNA Integrity Number (DIN/RIN) assessment
  • – Specific procedure for sample release: location check, quality sample check (volume, number of samples/amount of aliquots requested, anonymization code). In addition, for each tissue sample, a FFPE- or cryo-section is prepared, staining with Hematoxylin and Eosin and evaluated by a certified pathologist before transfer to the researcher. Diagnostic is then confirmed and if requested tumor cell percentage is determined.

The CRB-Tumorothèque ICO is certified NF S 96 900 (“Quality of biological resource centres (BRCs) – Management system of a BRC and quality of biological resources”) for the following activities: “Receipt, preparation and provision of cancer biological resources (tissues, fluids) from the tumor bank”.

Source of associated data

The demographical information (Gender, age) and clinical information (pathology report, treatment protocols, imaging, biological parameters, clinical follow up, etc) are available upon a specific request to the numeric data center associated with the CRB-Tumorothèque ICO and validation by the scientific advisory board.

Ethics Statement

The activities of the CRB-Tumorothèque ICO are in accordance with the French legislation (especially the law of bioethics, 7th July 2011, and the chapter IV of the Public Health Code that gather all regulations for biobanks). They meet the ethical and regulatory requirements that govern the collection, conservation and use of biological samples for scientific purposes; this includes, according to article L.1243-3 of the Public Health Code, approval of the collection from a competent research ethics committee (CPP, “Comité de protection des personnes” in French) and obligation to respect donor’s informed consent in any access request to the samples. In addition, the CRB-Tumorothèque ICO works in respect to the national ethical chart reedited in 2010 [4]. All samples processed by the CRB-Tumorothèque ICO were subject to the donor’s agreement and the signing of informed consent. The CRB-Tumorothèque is committed to destroying samples and related information at the request of the donor.

Researchers who would like to get access to bioresources available at the CRB Tumorothèque ICO must be compliant with the applicable law regarding their research projects and present legal/ethical authorisations/approvals required to the CRB upon request as a condition for granting access. As part of the access process, in addition to assessment of compliance with ethical and legal requirements, requests for assignments and accommodation are analysed on the relevance of scientific projects after validation by the scientific advisory board. All bioresources deposited at CRB-Tumorothèque ICO have been declared to and authorized by the French Research Ministry (Declaration Number: DC-2018-3321). This declaration includes approval by a research ethics committee (CPP).

Constraints

Available bioresources are composed by residual samples from patients who gave their agreement and have signed off the informed consent. External bioresources can be hosted by the CRB-Tumorothèque ICO upon request and validation by the scientific advisory board.

(3) Bioresource description

Object name

Centre de Ressources Biologiques – Tumorothèque ICO

Bioresource name

Centre de Ressources Biologiques – Tumorothèque at the Institut de Cancérologie de l’Ouest

Bioresource acronym: CRB-Tumorothèque ICO

Bioresource location

Institut de Cancérologie de l’Ouest

Boulevard Jacques Monod

44805 Saint-Herblain

France

Bioresource contact

CRBICO@ico.unicancer.fr

Identifier used

N/A

Bioresource type

CRB-Tumorothèque ICO is a clinical biobank dedicated to the preservation of biological samples from oncology patients.

Type of sampling

Biobank including Disease-based samples, longitudinal cohort, sampled in a research protocol.

Anatomical site

Tissues and biological fluids from various tumor types and anatomical site are available.

Disease status of patients/source

Oncological patients.

Clinical characteristics of patients/source

Adult and pediatric tumor samples with full clinical data de-identified before release. Clinical data are associated to each biological sample. Their access requests a specific application to the numeric data center associated with the CRB-Tumorothèque ICO and a validation by the scientific advisory board which serves as a formal Institutional Review Board.

Size of the bioresource

CRB-Tumorothèque ICO is a research infrastructure of the Institut de Cancérologie de l’Ouest dedicated to translational research and all collections are ongoing and have no definite end date. The collections contain currently (January 2020) around 100.000 biological samples originating from different research projects in collaboration with multiple researchers and physicians and are enriched by around 10.000 new samples each year.

Vital state of patients/source

Patients are alive at the time of sample collection. Patients are the source of clinical diagnoses.

Clinical diagnosis of patients/source

Eight biocollections are identified: Breast-Gynecology; Genitourinary system; Digestive system; Nervous system; Sarcomas; Aerodigestive track; Endocrinology; Hematology.

Pathology diagnosis

Variable

ICD-O M8000/0-M9989/3

Control samples

For tissue samples of the same organ both tumor and tumor-free tissue material macroscopically assessed are collected when possible.

Biospecimen type

CRB-Tumorothèque ICO can provide a large variety of biospecimens including serum, plasma, DNA, RNA, ascites, FFPE and fresh frozen tissues and Tissue Microarrays.

Size of the bioresource

The number of full time employees working at the CRB-Tumorothèque ICO is 10.

Release date

Samples and data are available since the 1st July 2018 upon request.

Access criteria

For any research group, a formal brief application is required (objectives, short description of samples, methods, data needed, timetable, associated funding) (Figure 1). All applications are reviewed by the governance committees (technical committee of the CRB-Tumorothèque ICO that checks the feasibility of the project on the base of the sample availability and the scientific advisory board that takes the final decision of acceptance after analysis of the scientific relevance, project feasibility and conflicts of interests. Similarly, access to clinical annotations will require a formal application and the validation of the numeric data center as well as the scientific advisory board of ICO. After acceptance, a contract including the ethical chart and the conditions of release will be proposed to the applicants and sign off before sample processing (e.g. conditions of transfer, storage, use, publication of results, disposal of withdrawn material, and financial aspects). The financial contribution is determined with the applicants and depends on the number and nature of data/samples needed as well as the nature of the contract (e.g. collaboration with shared publication or IP). In all cases, the origin of the materials provided (CRB-Tumorothèque ICO, FR) must be indicated in any communications done by the applicants.

(4) Reuse potential

The reuse by the contracting research group of samples delivered is not permitted without the permission of the CRB-Tumorothèque ICO. Conventionally, samples delivered in excess will be sent back to the CRB-Tumorothèque ICO for traceability and destruction. Tissue and fluid samples stored in multiple aliquots can be used for various projects.