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CTRF Leadership Meeting. Cancer Genomics and Development. of Diagnostic Tools and Therapies. July 1, 2002. Institutional Partners. V C U. G M U. I N O V A. 6/03/02. Minutes. Corrections Approval.
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CTRF Leadership Meeting Cancer Genomics and Development of Diagnostic Tools and Therapies July 1, 2002 Institutional Partners V C U G M U I N O V A
6/03/02 Minutes Corrections Approval
Develop Infrastructure and Intellectual Property that Enhances the Competitiveness of the Partners for Clinical and Extramural Funds Principle Objective
Evaluate gene expression (and genetic changes) in human brain, ovarian, breast and hematopoetic cancers Link gene expression (and genetic changes) to clinical findings and clinical laboratory findings (including histopathological diagnoses) in a common database Evaluate linked data using bioinformatics Research Objective
FY02 Budget Rollover Report (M. Newsome)
Cost Share Expenses • Cost share expenditures not paid from cost share linked accounts must be documented using ‘In Kind/3rd Party Cost Share form’ obtained from Margie Booker’s office. (http://www.vcu.edu/finance/ In-kind%20Cost%20Sharing%Certification.pdf)
Justification (Transaction Brief) • Reason for year-end balance • Project began late • Delay in recruitment of key personnel • IRB approval • Need for carry-forward funds • Use of the unexpended funds are essential to continue the project and carry out the programmatic aims of the grant • Matching funds have already been obligated • No alternative funds • How the funds will be used • Personnel • Supplies/Maintenance/travel
FY 03 Allocation • [Submit record of expenditures and matching funds (FY02 Closeout)] (Mike Newsome) • Progress Report indicating milestones achieved sent to Mike Newsome • Need to spend down carry over before new appropriations justified (J. Heiman)
Website Update www.ctrf-cagenomics.vcu.edu • “News & Updates” page added • Focus Group roles and responsibility still needed from Focus Group Leaders • Pages have been amended and new links have been added
SPIN Research • Jo Ann Breaux receiving daily notices of grant opportunities • Compiling weekly document of relevant findings • Will be distributed over the CTRF LISTSERV • SMART documents currently on the CTRF website • Training is available: http://www.InfoEd.org/default.stm
Focus Group • Tissue Bank • Clinical and Pathology Laboratory Data • Database Design • Data Analysis • Quality Assurance in Microarray Analysis • (Chip Fabrication - proposed)
IRB approval at INOVA Tissue Acquisition person to be hired and managed by Marianne Smith Inova to work out process for obtaining necessary informed consent Tissue Bank person to go to OR area with pathologist responding to request for frozen section and take tissue at that time Ideal procedure is unclear at this time for tissue acquisition unclear: Cut and freeze a piece of tissue at the OR (most rapid) Perform a frozen section on a block and then drop the latter into liquid nitrogen (delay 5-10min) Protocol handling for Bone Marrow Aspirates not yet specified Tissue is not to leave Inova until surg path written report is completed INOVA -CTRF - Tissue Bank
VCU - Tissue Bank • TAS approved by IRB 4/15/02 • Tissue Bank Staff Activities (Cynthia Losco) • Procedures Established in Main OR and Ambulatory Surgery • Cynthia to be notified 30 minutes before specimen to be ready on cases identified for CTRF eligibility • In-service given to OR staff to address new procedure • Bone Marrow Biopsy patients are being consented directly after procedure
Tissue Acquisition Database • Access Database • Computer has been installed at VCU • Database has been installed on machine at VCU • PC Anywhere software sent to Inova • To Contain Inova and VCU Cases
Tissue Utilization(1) • Non-anonymized tissue samples are a form of patient medical record • The health system where the medical record is created is responsible for access and integrity. • Personal identifying information should be maintained behind a health systems firewall.
Tissue Utilization(2) • Each health system which creates non-anonymized human tissue sample banks will: • Identify a guardian who is responsible for maintenance of the integrity of the collection and monitoring utilization. • Establish a tissue utilization committee to formulate criteria for use of samples.
Institutional Tissue Utilization Committee • Formulate criteria for who is eligible to obtain human residual samples at the institution. • Faculty status, IRB approval, ?scientific validity • ?minimum QA requirements • ?minimum data access requirements • Review requests for human tissue utilization. • Formulate criteria for the degree of clinical information which can be provided with the samples. • Assess resources required to fill request and whether PI is prepared to provide them.
Tissue Utilization(3) • For purposes of regulating utilization of all samples collected by CTRF tissue collection personnel for the CTRF Ca Genomics Project, it is assumed that: • the VCU and Inova tissue utilization committees agree to follow the criteria and decisions regarding tissue utilization as determined by the CTRF Ca Genomics Project Tissue Utilization Group.
Project Pis Garrett Buck Ginder Guiseppi-Eli Cooper Chandhoke Tissue Guardians Nasim Grant Cook Clinical Data Leadership Penberthy Smith Quality Assessment Leadership Ferreira-Gonzales Christensen Taylor Issues QA Program Pre-Analytical Tissue Handling Storage Conditions (Freezer Monitoring, etc) Manner in which tissue is supplied Storage and availability of data CTRF Ca Genomics Project Tissue Utilization Group
Tissue Utilization Summary VCU Tissue Committee Inova Tissue Committee CTRF Tissue Utilization Group Analyze Samples
Clinical Data Elements Define minimal set of common clinical data elements; Initial choice to be the elements required to be sent to state cancer registry Data elements should include MIAME (Minimum Information about a Microarray Experiment) for holding Expression Array Data GeneX Database – Initial choice for storing project data Database Design/Clinical Info
Database Design/Data Analysis • GeneX Database (Update) • Version 1.5 UVA (Jae K. Lee) • Version 2.0 GMU-VT (J. Weller) • “Terabyte” Database – (Update) • GMU • LabBook (Update - Buck) • VCU
QA/QC • Schema (VCU Preliminary) • 16 Chips • Test for Variation • Chip-Chip • Labeling • Buffers • Modules (4) • Update – VCU/GMU
QA/QC – GMU Update • GMU cDNA Microarrays • Check by hybridizing slides from each batch • Composite probe - one cDNA from each plate • Sequential cDNAs selected • 1A1, 2B2, 3C3, etc. • Labeled with fluorescent primer (FAM) and PCR • Hybridize and scan • Compare patterns: experimental vs. Expected
RNA Checked on gels Amplified RNA also checked Probe labeling Determine incorporation of fluorescent dye ~5,500 cDNAs printed one one microarray Four printings - ~200 slides ~40,000 cDNAs printed on two slides ~20,000 cDNAs per slide 80 slides of each printed ~50 microarrays (~5500cDNAs) hybridized reference RNA (Stratagene) experimental RNA Quality control - microarray manufacture Correct orientation and sequence of plates at all steps in manufacture process? QA/QC – GMU Update
QA/QC – VCU Update • VCU/MDx quality control: • chip/chip, run/run, fresh/frozen cRNA variation • Human Reference RNA (Stratagene) • 200 mg total RNA from 10 human cell lines • (additional aliquots to be shipped to GMU) Run day#2 Total Run day#1 • 4 chips/ fresh cRNA • 4 chips/ frozen cRNA • 4 chips/ frozen cRNA • 4 chips/ frozen cRNA 16 chips
QA/QC – VCU Update Quality Control Parameters • Sample Quality: • Bioanalyzer (28S/18S ratio) • Spectrophotometer (A260/A280) • 3’/5’ ratio for high abundant transcripts (GAPDH) • 3’/5’ ratio for low abundant transcripts (ISGF3A)
QA/QC – VCU Update Preliminary analysis Sample Quality: Bioanalyzer (28S/18S ratio) 3’/5’ ratio (GAPDH)3’/5’ ratio (ISGF3A) 1.83 1.09 3.68 0.76 9.36 1.06
QA/QC – VCU Update Quality Control Parameters Chip Performance: • Noise (RawQ) • Scaling Factor (SF) • Number of Present genes (P/A) • Spike controls Linearity (BioB, BioC, BioD, CREX) • Signal intensities for housekeeping genes (GAPDH, b-actin)
QA/QC – VCU Update Preliminary analysis Chip Performance:
QA/QC – VCU Update Preliminary analysis • Spike controls Linearity (BioB, BioC, BioD, CREX) • Run day#1Run day#2
CTRF - Promoting Focus Group Activity • Establish Standing Weekly or Biweekly Meeting Dates and Times • Complete the Milestone Updates • Document Discussions and Progress Using Listservs
Communication Amongst Members and Focus Groups 8 - LISTSERVS • CG-TISBK: Tissue Bank • CG-CLNDT: Clinical and Pathology Data • CG-DBDSN: Database Design • CG-ANLDT: Analyze Data (Data Analysis) • CG-QAQC: QAQC • CG-LDRPI: Focus Group Leaders and PIs • CG-MEMBS: All Members • CG-FBCHP: Chip Fabrication
LISTSERVS • Address messages to: listname@VENUS.VCU.EDU • Unsubscribe to the listserv by submitting a message with the words SIGNOFF listnameto: LISTSERV@VENUS.VCU.EDU • Subscribe to the listserv by asking the PI with whom you work to submit your name and E-mail address to the Program Director (C.Garrett) • USE the listserv(s) to inform members of your activity or to seek advice from the members.
Old Business • New Business • Presentations by CTRF CaGenomic’s Members at Bioinformatic’s Symposium held on June 12-14, 2002
CTRF - Specific Reportables - - Reminder - - • Intellectual property reporting - licenses, patents, etc • Publications • New applications • CTRF Administrative office • will search for new funding opportunities (SPIN) • will collect CVs, other support, facilities, interest documents • goal - 4 - 8 million in D.C. from CTRF CG Project • 5/21/02 - 1 million (1yr) submission to VTSF (Penberthy-PI) • “Early Clinical Trials of Imaging Agents” –contract to permit the VCU Molecular Imaging Center to respond to subsequent specific RFPs for development of new imaging agents. • Any other discoveries • Federal money leveraged • Private research money leveraged • Advancement of technology and economic development in VA
Next CTRF Leadership Meeting Monday August 5, 2002 9:30AM