Report of IBDC Breakout Session on Clinical Samples and Mouse Models

							Report of IBDC Breakout
   Session on Clinical
  Samples and Mouse
         Models
       IBDC Conference
    FHCRC, Seattle, WA, USA
        12 October 2005
                        Participants
   Yu-Sun Chang (Chang-Gung      Cheolju Lee (KIST)
    U)
                                  Lance Miller (GIS)
   Judith Clements
    (QueenslandUTSLS)             Hal Moses (Vanderbilt)
   Michael Davis (FHCRC)         Nallisivam Palanisamy
                                   (GIS)
   Ken Evans (OCBN)
                                  Incheol Shin (Hanyang U)
   Michael Gillette (Broad)
                                  Khay-Guan Yeoh (U
   Chris Kemp (FHCRC)             Singapore)
   Jeong Heon Ko (KRIBB)
                    Mandate
   “The clinical members should identify best
    procedures for tissue procurement and handling.
    The mouse experts should identify best mouse
    models for human cancer and optimum
    experimental paradigms for identifying mouse
    biomarkers for disease and cross correlating
    them with human biomarkers.”
               Mouse Models
   “Eliminate Red Herrings”
   FHCRC (McIntosh / Paulovich / Kemp)
    dedicated to defining ideal characteristics of
    mouse models, sample acquisition, storage,
    processing
   FHCRC standards and protocols available from
    Chris Kemp (cjkemp@fhcrc.org)
                          Sample Materials
   Need for best practices and detailed protocols
   Prospective Collection
   Blood products
       Plasma
       Serum
   Urine
   Tumor tissue
       Representative sections for HP review
       Details per tumor type & project requirement
            “Pure” tumor vs. tumor with margins
            Heterogenous tumors (prostate) especially difficult case
   Disease specific materials: “proximal fluids”
       Gastric Juice (gastric ca); Semen (prostate ca); pancreatic ductal lavage
        (pancreatic ca); CSF (CNS malignancy)
                              Plasma
   Ultimately BMs must survive vagaries of clinical
    laboratories
       Discovery particularly challenging; standards more rigorous
   Citrate or EDTA, not heparinized tubes
       Ideally single vendor, single lot
   Plan aliquots carefully at inception
       Available volume; requirements for intended applications;
        storage constraints; FT minimization
       Consider “moderate” initial aliquots, eg 0.5 – 1 mL, allowing
        single FT cycle for subaliquots
   -80° C standard for storage
                        All samples
   Barcoding from time of initial sample collection
   System should track all steps in sample handling &
    processing (21 CFR adherence)
   SOP adherence complemented by careful
    documentation of collection / storage parameters for
    each sample (stopwatch in OR)
   Samples may be used for initial validation as well as
    discovery
       Regulatory compliance: Agencies care about details
       *Rigorous adherence to GCP / GLP / GMP (Good Clinical
        / Laboratory / Manufacturing Practice)
   Controls critical
       Always imperfect; often inadequate
   Project-specific controls
       Minimize site / batch signatures
       Plasma requires “suitably matched” controls
            Healthy
            Confounding disease
       Tumor – consider multiple “orthogonal” controls
            Distant histopathologically uninvolved (“non-tumor”)
            Contralateral uninvolved (eg prophylactic mastectomy)
            Non-malignant diseased
            “Healthy”
            Other malignant
   The only missteps that are unrecoverable are those
    related to sample collection, storage, & annotation
   IBDC standing committee for sample collection &
    storage
       Review / incorporate / disseminate best practices &
        protocols
       ? Limited empiric assessment across consortium
   IBDC prospective longitudinal collection of carefully
    annotated plasma / urine samples dedicated to BM
    validation (cf Women’s health initiative, nurses health
    study)