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The Cooperative Human Tissue Network (CHTN): A Biospecimen Resource supported by NCI

The Cooperative Human Tissue Network (CHTN) supports basic and early translational research, including assay validation, since 1987. The network procures various types of tissue samples and extracts, as well as body fluids, which have been used in thousands of publications and patents. The CHTN has also supported the development of biomarkers, molecular assays, and patent applications.

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The Cooperative Human Tissue Network (CHTN): A Biospecimen Resource supported by NCI

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  1. The Cooperative Human Tissue Network (CHTN): A Biospecimen Resource supported by NCI https://www.chtn.org/ 17th Annual Principal Investigators’ Retreat, 2016 Innovative Molecular Analysis Technologies Program Rodrigo Chuaqui, MD Pathology Investigation and Resources Branch, Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis

  2. Cooperative Human Tissue Network (CHTN) Supports basic and early translational research, as well as assay validation since 1987 (Vand. U) (OSU) (U. Penn) (UVA) (Nationwide Children’s H.) (UAB)

  3. Tissue Samples and Extracts Procured by the CHTN 2005-2010 Fresh Frozen Paraffin Embedded/Blocks Tissue Microarrays RNA/DNA Nitrocellulose and Other Blots Other Malignant Preinvasive Neoplasia Uninvolved/Normal Benign Non-neoplastic Diseased Other • Blood • Buccal Mucosa • Buffy Coat • Lavage • Peripheral Effusion • Peripheral Blood • Plasma Body Fluids Procured by the CHTN 2005-2010 * • Serum • Sinus Contents • Sputum • Stool • Urine * Not all Divisions

  4. CHTN: Scientific Impact • 3,900 publications using CHTN samples • 268 patents issued since 1987 • Supports Basic/Discovery Phase Research (RO1, R21, R33) • Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection (Doitsh et al, Nature 2014) • Polyomavirus integration and Merkel tumor (Feng et al, Science 2008) • Single cell sequencing and tumor evolution (Navin et al, Nature 2011) • B-cell derived lymphotoxin promotes castration-resistant prostate cancer (Ammirante et al, Nature 2010) • Paracrine requirement for hedgehog signaling in cancer (Yauch et al, Nature 2008) • Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations (Pugh et al, Nature 2012)

  5. Examples of CHTN-supported Assays developed 1)Biomarkers in Serum -ErbB1 EGFR in ovary -CA125, apolipoprotein A-1, TTR, transferrin (TF) in serum in ovary -Protein Chips in ovary (N vs Tu, panels I and II vs grade and stage) -Mammoglobin in serum in breast -MUC1 in Pancreatic Cancer -CARE (cancer recognition Ab) in Tumors 2) IHC (tissues) -Anti-myogenin and MyoD1 in identifying rhabdomyosarcoma in trials -IHC in ovary: NASP, RCAS1, Nijmegen breakage syndrome 1 (NBS1), e1F5A, p53, Her2 3) Molecular in tissues: -Slot blot for telomere decreased content that correlates with prognosis in breast -Real time PCR for 17q gain and neuroblastoma and worse prognosis -5/12 microRNAs confirmed from tissue to plasma as potential biomarkers in non-small cell lung cancer

  6. Examples of CHTN-supported patent applications 1) FISH Probes -FISH (probes) in Cancer -ERB2 in Breast (copy #) -Copy # in cervical cancer 2) mRNA array profiles/signatures -General for cancer -Colon cancer 3) Epigenetics -Homeobox methylation in colon cancer -Others  4) MicroRNAs -Upregulation of microRNAs mir-221, mir-222 in teratoid and rhabdoid tumors as potential therapeutic targets 5) Technologies for RNA analysis in FFPE

  7. Biopecimens for Biomarker/Technology Development PipelineCancer Diagnosis Program, DCTD Assess assay performance in context: reproducibility, sensitivity, specificity, etc. Assess feasibility of detection/assay technology and marker prevalence Final late stage development, assay qualification, validation Test cut-points in new retrospective specimen set CHTN Set preliminary cut-points Test biomarker in retrospective set of specimens Marker/ technology discovery Clinical Trial activation

  8. 17th ANNUAL IMAT PI MEETING 2016Session on Advancing Clinical Capabilities: Diagnostics and Treatment Rodrigo Chuaqui, MD and Lokesh Agrawal, PhD Cancer Diagnosis Program, DCTD, NCI

  9. MAIN ISSUEGetting from Research Data to the Clinical Arena Assess assay performance in context: reproducibility, sensitivity, specificity, etc. Assess feasibility of detection/assay technology and marker prevalence Final late stage development, assay qualification, validation Test cut-points in new retrospective specimen set Set preliminary cut-points Test biomarker in retrospective set of specimens Marker/ technology discovery Clinical Trial activation

  10. Challenges in Clinical Biomarkers Discovery and Validation (Integral and Integrated) • Regulatory issues (sample procurement, clinical validation) • Lack of harmonized Biospecimen workflow/sample preparation procedures • Molecular Heterogeneity • Patient variability • Technology Limitations (Cost, time-consuming, analytical performance, etc)

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