Programme 9 : Biobaking

Programme 9 : Biobaking

PROGRAM LEADERS

Pr Anne COUVELARD (MD, PhD), Professor of Pathology at Université Paris Cité, is the Head of the Pathology Department, Hôpital Bichat – Claude-Bernard, DMU DREAM, APHP Nord. She is specialized in digestive pathology, and her main topics of research are pancreatic and neuroendocrine oncogenesis and the relationship between tumour progression, pathology and genetics. Translational research projects are developed in the Pathology Department, based on biobanking of tissue samples associated with clinical data, and on the development of tools to localize in situ and quantify molecular markers.

Pr Jérôme CROS, is a Professor of Pathology at the Beaujon Hospital – Université Paris Cité, Clichy-France, an ENETS center of excellence and the largest French pancreatic surgical center. He heads the pancreatic pathology and leads a research group dedicated to (i) the study of pancreatic tumors focusing on tumor heterogeneity and chemotherapy-induced clonal selection, (ii) the development of innovative tools (AI, MALDI imaging…) to subtype tumor according to their molecular profile.

HEALTHCARE EXECUTIVE

Véronique COLMANT
P9 chiffres clés

STRENGTHS IN THE FOLLOWING AREAS

Cancer Care:

 

13 structures are involved in biobanking in our Cancer center, located in 5 sites (Beaujon (BJN), Bichat – Claude-Bernard (BCH), Lariboisière – Fernand-Widal (LRB), Saint-Louis (SLS), Robert-Debré (RDB): 5 pathology departments (tissue biobanking), 4 biological resource centers (CRB) (non-tissue biobanking), 3 genetic departments (biobanking of RNA-DNA from solid or hematological tumors), 1 biological hematology department (blood and bone marrow/RNA-DNA biobanking). All facilities for cryopreservation (4 cold rooms, n=58 -80°C freezers, large liquid nitrogen tanks, n=14 -20°C freezers and one -150°C freezer) are available in all sites, with computed security follow-up of cold temperatures, computed archival systems for tissues, cells and blood-derived samples. One strength of these annotated collections is to cover most of all solid tumors and hematological malignancies.

Pathology departments handle frozen tissues and formalin-fixed paraffin embedded (FFPE) tissues coming from patient care (biopsy samples or surgical samples sent to the pathology department for diagnostic purposes). The CRB-tissue banks in the pathology departments ensure the preparation, storage, monitoring and transfer of human samples tissues from different organs (tumor and non-tumor). A digital database ensures the traceability of tissue samples from their reception to their expedition for care/research purposes. Our staffs, including qualified technicians and senior managers, are competent for the management of such samples according to the regulatory laws. Technical facilities include the production of tissue sections used for molecular biology and / or blank slides, either from FFPE and frozen tissue, protein lysates or nucleic acids. The tumor / non-tumor nature and the quality of the samples (% of tumor cells, necrosis) are systematically verified by a pathologist. The frozen samples are kept within each pathology department, in -80 ° C freezers, with H24 temperature monitoring system and a technician on call. Tissues (either FFPE or frozen) are available from each pathology department for patient care and can be transferred to genetic departments following molecular tumor boards requests (see OECI / GT6 genomic of tumors) for diagnostic, prognostic and theranostic genomic analyses needed by oncology routine care. The Genetics department is performing these analyses depending on the oncology specialties for specific tests (mainly oncothoracic, oncodermatology, oncodigestive, neuro-oncology and gyneco-oncology…). For 2nd line high throughput testing, frozen samples can be dispatched to the SeqOIA platform for whole genome/exome sequencing. Such WGES/WES is performed for patients with hematological cancers included in the France Médecine Génomique 2025 plan (PFMG2025) for Refractory or relapsing acute Leukemia in adult, and results are discussed in the national MDT coordinated by R. Itzykson and E. Clappier at Saint-Louis hospital.

Nearby pathology departments CRB “Biological Ressource Centers” (or BRC) are involved in biobanking of non-tissue samples (blood, serum, plasma, DNA, RNA, cells and organoids…). These samples are obtained from specific research projects.

The CRBs aim to organize collections of biological samples of good quality in order to support clinical and translational research projects for all clinical and research teams of the Cancer Center. Their missions are i) to ensure the collection, transformation and conservation of human biological samples using quality benchmark, ii) advise and support the creation of biological collections (methodology, regulations, biology, logistics), iii) to promote the use of collections, their sharing and collaborations between research teams, iv) to ensure the compliance with bioethics laws. Researchers’ requests for biological samples are examined by the scientific board of each collection. Once the project is validated, the samples can be sent after anonymization. In addition, the CRBs offer scientific support and technical services for analysis of the samples by a multidisciplinary team composed of pathologists, molecular biologists, biochemists, cell biologists, and biophysicians.

There is a specific organization of the CRB-BCH, serving for the CRB for the 3 sites LMR, BJN, BCH. Several daily shuttles dedicated to the samples transport are organized between Beaujon and Bichat – Claude-Bernard and between Louis-Mourier and Bichat – Claude-Bernard.

Samples from hematological cancer patients (mainly bone marrow and blood samples) are received as part of care for patients having various hematological malignancies treated at Saint-Louis hospital or in other clinical centers. In addition, samples from patients enrolled in trials for treatment of acute lymphoblastic leukemia (ALL) treated in centers across France, Belgium and Switzerland are centralized for care and research purposes. All these samples are primarily sent for molecular analyses, either at diagnosis or relapse to identify diagnostic, prognostic or theranostic markers, and during follow-up to perform minimal residual disease analyses. The Molecular Hematology team within the OncoHem-SLS receives samples, perform cell isolation, DNA/RNA purification and molecular analyses. Molecular analyses include Next-Generation Sequencing with various gene panels according to the malignancy and RNA-seq. Results are discussed in several molecular tumor boards for different hematological malignancies: local MDTs for acute leukemias, for myelodysplastic syndromes, for myeloproliferative neoplasms, etc and a national MDTs for inherited hematological malignancies, coordinated by M. Sébert and E. Clappier at Saint-Louis hospital.

Lastly for pediatric cancers at RDB, samples are received as part of care for pediatric leukemia (mainly bone marrow and /or blood) are handled by the molecular genetics laboratory team. Only the derived products (mainly extracted nucleic acids and frozen cell pellets) are stored. All diagnoses and relapses received at Robert Debré from different pediatric Onco-Hematology clinical services across France (The main prescribers are: Robert-Debré, Besançon, Caen, Dijon, Grenoble, La Réunion, Martinique, Montpellier, Nantes, Nice, Strasbourg and Saint-Etienne) are the subject of an NGS sequencing on ​​a targeted panel including all diagnostic / prognostic / theranostic alterations known in leukemia. RNAseq analysis is also performed for approximately 100 patients / year. These same samples are used for sequencing on the SEQOIA and AURAGEN WGS platforms if the patient is included in the FMG2025. For RDB patients, such results are systematically discussed since 2019 in local molecular MDTs, every two weeks. With the rise of FMG2025, this MDT will be opened in November 2021 at the national level.

Research:

Number of PHRC, PRTK, PLBIO, PRIME, ANR, CLIIP, AAP ARC, ligue contre le cancer, FRM, GEFLUC, PAIR:

  • AAP Physics & cancer INCa
  • PAIR Pancreas
  • PRTK MOSAPAC
  • PRTK Lung cancer and lung fibrosis
  • EORTC 58 081 (547 samples)
  • EORTC 58591 (605 samples)

Number of FHU, SIRIC, RHU:

  • FHU MOSAIC,
  • RHU OPERANDI

Basic science:

  • UMR Inserm 1149
  • UMR Inserm 1152
  • UMR Inserm 976
  • UMR Inserm 7513
  • U Inserm 944
  • UMR Inserm 965
  • UMR Inserm 1141

Education:

The integration of images into biobank creates a unique repository for educational purposes (see below). Through the FHU MOSAIC, we have already put in place a recurrent joined teaching seminar between pathologists and radiologists on liver diseases. These seminars are using the proof-of-concept database with linked multimodal images hosted by EDS. The development of well annotated image collections will favor similar initiatives. We envisioned that these collections can also be used for self-training throughout the professional life and for medical student/resident exams.