Cancer Care:

 

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

Pathology departments handle frozen tissues and formalin-fixed paraffin embedded (FFPE) tissues originating from patient care (biopsy samples or surgical samples sent to the pathology department for diagnostic purposes). The CRB-tissue banks within the pathology departments ensure the preparation, storage, monitoring, and transfer of human tissue samples from different organs (both tumors and non-tumors). A digital database ensures the traceability of tissue samples from their reception to their expedition in view of 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 or blank slides, either from FFPE, frozen tissues, protein lysates or nucleic acids. The tumor / non-tumor nature, as well as the quality of 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 a 24-hour temperature monitoring system and a technician on call. Tissues (either FFPE or frozen) are available from each pathology department for patient care; they can be transferred to genetic departments following molecular tumor board requests (see OECI / GT6 genomic of tumors) for diagnostic, prognostic, and theranostic genomic analyses required in view of routine oncology care. The Genetics department performs these analyses depending on the oncology specialties for specific tests (mainly of oncothoracic, oncodermatology, oncodigestive, neuro-oncology, or gyneco-oncology nature). For second-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 adults, and results are discussed in the national multidisciplinary team (MDT) that is coordinated by R. Itzykson and E. Clappier at Saint-Louis hospital.

Nearby pathology departments of Clinical Resource Centers (CRCs) or Biological Resource Centers (BRCs) are involved in bio-banking of non-tissue samples, including blood, serum, plasma, DNA, RNA, cell, and organoid samples. These samples are obtained for 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 multifold: 1) to ensure the collection, transformation, and conservation of human biological samples using quality benchmarking; 2) to advise and support the creation of biological collections regarding methodology, regulations, biology, and logistics; 3) to promote the use of sample collections and their sharing, as well as collaborations among research teams; 4) to ensure the compliance with bioethics laws. Researchers’ requests for biological samples are examined by the scientific board of each collection. Once the project has been validated, the samples can be sent after anonymization. In addition, the CRBs offer scientific support and technical services for sample analysis by a MDT composed of pathologists, molecular biologists, biochemists, cell biologists, and bio-physicians.

There is a specific organization of the CRB-BCH, serving for the CRB of the three sites involving LMR, BJN, and BCH. Several daily shuttles dedicated to the samples’ transport are organized between Beaujon and Bichat, and between Louis Mourier and Bichat, as well.

Samples from hematological cancer patients, mainly consisting of bone marrow and blood samples, are received as part of patient care for those suffering from various hematological malignancies treated at Saint-Louis hospital or in other clinical centers. In addition, samples from patients enrolled in clinical trials for managing 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 the time of diagnosis or relapse in order to identify diagnostic, prognostic, or theranostic markers, or during follow-up in order to perform minimal residual disease analyses. The molecular hematology team within the oncological-hematological service (OncoHem) at SLS receive the samples, and they then perform cell isolation, DNA/RNA purification, and molecular analyses. Molecular analyses include next-generation sequencing (NGS) with various gene panels according to the malignancy and RNA-seq. Results are discussed in several molecular tumor boards for different hematological malignancies, including local MDTs for acute leukemia, for myelodysplastic syndromes, for myeloproliferative neoplasms, and for others. A national MDT for inherited hematological malignancies is being coordinated by M. Sébert and E. Clappier at Saint-Louis hospital.

Lastly, for pediatric cancers at RDB, samples are received as part of patient care for those suffering from pediatric leukemia, mainly consisting of bone marrow or blood samples; these samples are handled by the molecular genetics laboratory team. Only the derived products, primarily comprising extracted nucleic acids and frozen cell pellets, are being stored. All diagnoses and relapses received at RDB from different pediatric OncoHem clinical services across France, with the main prescribers  being Robert Debré, Besançon, Caen, Dijon, Grenoble, La Réunion, Martinique, Montpellier, Nantes, Nice, Strasbourg, and Saint Etienne, all undergo NGS sequencing on ​​a targeted panel that include all the diagnostic / prognostic / theranostic alterations so far known in leukemia tumors. RNAseq analysis is also performed for approximately 100 patients each year. These same samples are used for sequencing on the SEQOIA and AURAGEN WGS platforms given that the patient is included in the FMG2025. For RDB patients, such results have been systematically discussed since the year 2019 in local molecular MDTs, every two weeks. With the rise of FMG2025, this MDT has been opened at the national level in November 2021.