Biobanking for Precision Medicine Seminar Series

Mini-series on the theme of biospecimen science.

• April 24, 2024

  Dr. Muhammed Murtaza: Preanalytical considerations for Analysis of Circulating Tumor DNA
  Abstract: Analysis of circulating tumor DNA in plasma has transformed genotyping for actionable mutations in patients with metastatic cancer. Recent and ongoing studies are evaluating the potential utility of ctDNA analysis for early detection, residual disease detection and monitoring for recurrence. Unlike metastatic cancer, ctDNA levels in patients with early stage cancers are generally much lower, making these applications more susceptible to preanalytical variation. In addition, unlike somatic mutation analysis, new approaches investigating tumor-derived features in plasma DNA such as fragmentation patterns, end-motif signatures and methylation are not fundamentally tumor-specific. Most studies rely on complex computational approaches to infer tumor contribution based on these features, and the impact of preanalytical variation on these assays remains unknown. As methods for ctDNA analysis evolve and we look beyond the early achievements of this field, new opportunities to improve accuracy, ease of use and equitable access can arise through careful investigation of biospecimen handling and processing. In this talk, I will review current knowhow and demonstrate recent advances arising from the study of preanalytical factors affecting ctDNA analysis.

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  May 30, 2024

  Dr. Joanna Phillips: Defining Critical Preanalytical Variables for Translational and Clinical Research in Diffuse Glioma
  Abstract: Diffuse glioma, including IDH-wildtype glioblastoma (GBM) and IDH-mutant diffuse glioma, are characterized by an aggressive clinical course. Despite advances in our knowledge of genetic and epigenetic alterations, many targeted therapies for GBM have failed. Determining the cause for such failures is critical. Pharmacodynamic biomarkers in window of opportunity clinical trials are tools that can provide important information on target engagement. Given its importance in diffuse glioma, phosphatidylinositol 3 (PI3)-kinase/AKT/mTOR (PI3/AKT/mTOR) signaling is an attractive therapeutic target. Yet, the relevant preanalytical variables and optimal tumor sampling methods necessary to measure pathway activity are unknown. To address this, we used a murine model for IDH-wildtype glioblastoma (GBM) and human tumor tissue, including IDH-wildtype GBM and IDH-mutant diffuse glioma. First, we determined the impact of delayed time-to-formalin fixation on the quantitative assessment of cellular expression of six phosphoproteins that are readouts of PI3K/AK/mTOR activity (phosphorylated -proline-rich Akt substrate of 40 kDa (p-PRAS40, T246), -mechanistic target of rapamycin (p-mTOR; S2448); -AKT (p-AKT, S473); -ribosomal protein S6 (p-RPS6, S240/244 and S235/236), and -eukaryotic initiation factor 4E-binding protein 1 (p-4EBP1, T37/46). With delays of ≥2 hours, typical of routine clinical handling, all had reduced or altered expression with p-RPS6 (S240/244) exhibiting relatively greater stability. A similar pattern was observed using patient tumor samples from the operating room with p-4EBP1 more sensitive to delayed fixation than p-RPS6 (S240/244). Many clinical trials utilize unstained slides for biomarker evaluation. Thus, we evaluated the impact of slide storage conditions on the detection of p-RPS6 (S240/244), p-4EBP1, and p-AKT. After 5 months, storage at -80ºC was required to preserve the expression of p-4EBP1 and p-AKT while p-RPS6 (240/244) expression was not stable regardless of storage temperature. Ongoing tumor evolution can drive striking regional heterogeneity in tumors such as in glioma. Tumor sampling and intratumoral heterogeneity is a critical factor that needs to be addressed for any biomarker. The UCSF Brain Tumor SPORE Biorepository has acquired multiple regionally distinct human tumor samples that represent maximal tumor sampling from patients with diffuse glioma. Quantification of p-RPS6 (240/244) expression in these tumor samples from eight patients revealed significant intratumoral heterogeneity. Thus, the accurate assessment of PI3K/AKT/mTOR signaling in diffuse glioma must overcome both intratumoral heterogeneity and multiple preanalytical factors, including time-to-formalin fixation, slide storage conditions, and phosphoprotein of interest. In addition, challenges related to biobanking and annotation of biospecimens and the importance of strict standard operating procedures for biorepositories will be discussed.

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  October 22, 2024

  Dr. Michael Roerhl: Precision Pathology: Next Gen Biobanking Drives the Future of Multiomic Theranostics in Cancer
  Abstract: The future of precision healthcare depends crucially on new biomarkers for early diagnosis, drug target development, treatments response monitoring, and resistance detection. Forward-looking and future-proof biobanking in pathology is a key prerequisite in this endeavor. We will discuss examples from both tissue-based and liquid-based biobanking that is tailored for optimal biomarker evaluation, quality control, and transitioning from discovery research to clinical application for the benefit of cancer patients. Examples include single- and multiplex detection of immune checkpoint proteins and integrated proteogenomics and phosphoproteomics in cancer types such as colorectal cancer, neuroendocrine tumors of the pancreas, or lung cancer. Next Generation Biobanking is the key for improving patients' lives everywhere. We propose hospital-based Clinical Centers of Biobanking Excellence in Pathology as a strategy to get us there.

Mini-series on the theme of data sharing in biobanking studies and research that uses biospecimens.

• September 11, 2023

  Dr. Jaime Guidry Auvil and Dr. Emily Boja: From Biospecimen to Data and Knowledge: Driving Impactful Resource Sharing for Cancer Research
  Abstract: The National Cancer Institute (NCI), in line with US government policies, strongly advocates for equitable data sharing and collaborative science across the cancer research community for the benefit of those afflicted with or at risk for the disease. With modern technology and tools, experts can glean powerful insights from high quality, structured data associated with biospecimens used for research exponentially faster and more accurately than ever before. Through the studies it funds, NCI collects high-quality biospecimens and associated data, multiple types of clinical care, population studies and scientific research data that collectively can provide a comprehensive understanding of cancer subtypes, inform therapeutic strategies and promote public health. To this end, NCI has established an Office of Data Sharing (ODS) focused on developing and implementing an approach to data sharing that maximizes utility of diverse data types across cancer studies in line with government policy expectations and regulations. Drs. Guidry Auvil and Boja, from ODS, will discuss the vision and direction of data sharing for NCI studies that use biospecimens, including how key data initiatives can provide a framework of data assembly, infrastructure and utility that are aimed at bridging patient care, public health and cancer research through aligned and consistent approaches to data sharing.

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  October 18, 2023

  Dr. Veena Gopalakrishnan, Anita Mohandas and Dr. Mark Jensen: Data Management for NCI’s Cancer Moonshot Biobank — A Case Study
  Abstract: Biospecimens of known quality and associated well-annotated data are an essential resource for cancer research. To support research in drug resistance and sensitivity, NCI’s Cancer Moonshot Biobank study collects pre- and post-treatment biospecimens from patients who have solid or hematological malignancies and are undergoing standard of care treatments. An integrated IT infrastructure facilitates the collection, storage, management, and distribution of clinical and biospecimen data, radiological and histological images, and genomic sequencing data. The study’s clinical data management system is integrated with the patient registration system, electronic consent application, and biorepository LIMS that records detailed biospecimen processing and inventory data. Clinical assay results are returned to research participants and their medical providers through a secure online engagement website. A research data product was envisioned to provide researchers with an integrated dataset in addition to the associated biospecimens. An in-house data management environment was developed to transform raw data files using customized scripts to remove Personally Identifiable Information (PII) and present data in a consistent format. The data is normalized while maintaining integrity and consistency so that it is readily usable for data analysis. The study data is shared incrementally via NCI-designated public databases through controlled access.

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  November 15th, 2023

  Dr. Alan Hutson, Dr. Tao Liu and Dr. Alex Lash: Data Management and Sharing in Cancer Moonshot Data Coordination Centers for IOTN, DRSN/ARTNet, and HTAN
  Abstracts:
  Case Study by Drs. Hutson and Liu: Enhancing Data Sharing and Dynamic Visualization — Strategies and Tools from an NCI-Funded Coordinating Center Perspective
  In this talk we will unveil the latest strides in data sharing, software distribution, and model dissemination, all viewed through the lens of a coordinating center. We will provide an overview of data visualization tools and strategies that have taken shape within the Cancer Moonshot℠ Immuno-Oncology Translational Network (IOTN) Data Management Resource Center (DMRC) and the Acquired Resistance to Therapy Network (ARTNet) Coordinating Center.

  Case Study by Dr. Alex Lash: HTAN Data Coordinating Center
  For the last five years, the Data Coordinating Center (DCC) for the Cancer Moonshot Human Tumor Atlas Network (HTAN) has been responsible for managing, organizing, curating, and disseminating the data and resources generated through the network. The DCC provides key services to support the Research Centers that comprise the network, and to foster a community based on collaboration, transparency, and sharing. The DCC’s primary scientific objective is to accelerate the discovery of mechanisms governing tumorigenesis, progression, and evolution, which will lead to improved prevention and treatment strategies for patients. The DCC achieves this objective by providing technology services coupled with best practices to expedite data acquisition and dissemination to HTAN researchers, as well as the broader scientific community. HTAN data is available for download and visualization in the HTAN Data Portal, NCI’s Cancer Data Cancer Research Commons (CRDC) data repositories, and several outside tools specifically designed for the visualization of spatial proteomics and single cell transcriptomics data.

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  December 13th, 2023

  Dr. Sheri Schully: Data Management and Sharing in the All of Us Research Program
  Abstract: The All of Us Research Program is enrolling a diverse group of at least 1 million persons in the United States in order to accelerate biomedical research and improve health of individuals and populations. The program aims to make the research results accessible to participants, and it is developing new approaches to generate, access, and make data broadly available to approved researchers. All of Us opened for enrollment in May 2018 and currently enrolls participants 18 years of age or older from a network of more than 340 recruitment sites. Elements of the program protocol include health questionnaires, electronic health records (EHRs), physical measurements, the use of digital health technology, and the collection and analysis of biospecimens, including genetic analysis. To date, the program has enrolled over 700,000 participants with whole genome sequencing data is available to researchers on more than 245,000 participants.

Mini-series on “Creating biobanking infrastructures that enable return of results.”

• February 16, 2022

  Dr. Shannon McCall: Next Generation Biobanking: Operational and Regulatory Requirements for Reporting Results Clinically
  Abstract: During this talk, Dr. McCall will briefly review the creation and goals of the Clinical Laboratory Improvement Amendments of 1988 as well as the relevant definitions pertaining to reporting laboratory testing results clinically. She will discuss the pathways for obtaining a CLIA certificate and the spectrum of translational and clinical research activities in this context with an emphasis on tissue-based laboratory testing. The talk will conclude with operational and regulatory requirements invoked by specific activities and project goals concerning research.

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  March 29, 2022

  Dr. Nilsa Ramirez, Dr. Scott Jewell and Dr. Shannon McCall: Case Studies on Biobanking Infrastructures that Enable Return of Results: Part 1 and Part 2
  Abstracts:
  Case Study by Dr. Ramirez: Biobanking in the Context of Clinical Trials — The Biopathology Center Experience
  The Biopathology Center provides biobanking services to several NCI- sponsored clinical trial efforts (e.g., COG, SWOG, NRG Oncology, EET). For some of the clinical trials sponsored by these groups, it is necessary or required to support biospecimen processing in a CAP accredited/CLIA certified environment. Specimens processed under these regulatory requirements can be used for downstream clinical testing, patient stratification, and targeted treatments. This presentation will highlight our experience in this setting, including how our CAP BAP accredited research laboratory activities co-exist with our LAP accredited/CLIA certified clinical laboratory activities.

  Case Study by Dr. Jewell: The Cancer Moonshot Biospecimen Core Resource
  A biospecimen core resource performs an array of tasks to meet the biospecimen management needs of a research project. When research projects are based on human biospecimens from research participants, clinically relevant findings may arise either as part of the intended project or incidentally. Like many biobanks that are involved in clinical trials, the advancement of research technologies continues to push the need for biobanks to teeter between the research and clinical utility of patient samples. The Van Andel Research Institute serves as the biospecimen core resource (BCR) for the Cancer Moonshot Biobank, which conducts clinical biomarker assays for enrolled research participants. This presentation will discuss the organization, description of services and the design of the BCR to develop and maintain the capability for clinical testing results to be returned to patients

• February 24, 2021

  Dr. Helen Morrin: Becoming a Culturally Responsive Biobank: A Journey with the Indigenous Mâori People of New Zealand
  Abstract: New Zealand is bicultural and has an ethical, legal, and moral requirements to incorporate the indigenous Mâori people’s cultural values into the nation’s biobanking practices. With consultation, we have partnered and undertaken a 20-year journey with the Mâori to address concerns, such as:

  • The desire for tissue to remain in New Zealand.
  • Culturally appropriate tissue handling practices.
  • Specimen return or disposal with a karakia (blessing).

  The concept of collective ownership of genes and data, which presents extra challenges in the new era of globalization and databanks.

  This presentation will reflect on the biobank’s journey navigating key issues and look to the future. We will describe the culturally inclusive operational procedures that the biobank and its stakeholders have developed, both within the tertiary hospital and within the cancer biobank, that have assisted in Mâori being comfortable with donating their tissues and data and how Mâori guardianship is incorporated into all aspects of the biobank.

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  May 5, 2021

  Dr. Craig Shriver and Dr. Justin Wells: Development of the Department of Defense Biobank Network and the APOLLO Research Program

  Abstract: The Department of Defense (DoD), through the Murtha Cancer Center, has a wide-ranging biobank network that consists of DoD, Veterans Health Administration, and civilian sites, all of which are highly-coordinated and follow rigorous collection protocols to assure the highest quality of biospecimens and associated data for research. In this presentation, we will present various aspects of the administrative, resourcing, standard operating procedures, management, and research capabilities of the DoD biobank network.

• November 4, 2020

  Dr. Peter Watson: “Permission to Contact”: An Integrated Strategy for Patients and Scientists to Improve Engagement and Enrollment in Biobanking and Clinical Research
  Abstract: Approximately 40 percent of cancer research depends on human biospecimens and data that are collected through biobanking in the context of basic, translational, and clinical research studies and biobanks. The research demand for biospecimens is steadily increasing in terms of scale and scope. Therefore, improving the way (for patients and researchers) that we enroll patients into all clinical research that includes biobanking components is important. All research also depends on funding, and therefore improving the way we engage with, inform, and obtain the support of patients is also important. And yet in many cancer centers, only a small fraction of patients ever hear about research opportunities or are asked to participate. And those who do participate are usually enrolled into study-specific (personalized) databases that are hard for other researchers to find or access. This seminar presentation will describe an enrollment model to address these issues called a “Permission to Contact for Research” (PTC) platform which was developed in British Columbia, Canada. We will describe the implementation and performance of the PTC platform, and how it has proven to be efficient, effective and engaging for both researchers and patients.