1. CTRF Leadership Meeting July 1, 2002 Institutional Partners V C U G M U I N O V A

2. 6/03/02 Minutes Corrections Approval

3. Develop Infrastructure and Intellectual Property that Enhances the Competitiveness of the Partners for Clinical and Extramural Funds Principle Objective

4.  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

5. Funding From CTRF

6. FY02 Budget Rollover Report (M. Newsome)

7. Reminder - Cost Share Form (VCU)

8. Estimated Cost Share Account PI Account # Comm’d Cost Share (Direct Cost Only) Yr to Date as of 5/31/02 Variance Admin2-90000 97,50081,347(16,153) Garrett4-12310 326,595274,705(51,890) Guiseppi-Elie1-37100 217,950148,679(69,271) Buck1-30139 138,144124,375(13,769) Ginder4-12320 98,75048,548(50,202) Inova 211,070 GMU 177,226

9.  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. Cost Share Expenses (http://www.vcu.edu/finance/ In-kind%20Cost%20Sharing%Certification.pdf)

10. FATS Table

11. 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

12. 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 )

13. Website Update  “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

14. 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

15.  Tissue Bank  Clinical and Pathology Laboratory Data  Database Design  Data Analysis  Quality Assurance in Microarray Analysis  (Chip Fabrication - proposed) Focus Group

16. Focus Group Leaders

17. 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

18. 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

19. Specimens Acquired

20. Manual Form for Tissue Acquisition

21. Histopathologic Parameters

22. 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

23. 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.

24. Tissue Utilization(2)  Each health system which creates non-anonymized human tissue sample banks will: οIdentify a guardian who is responsible for maintenance of the integrity of the collection and monitoring utilization. οEstablish a tissue utilization committee to formulate criteria for use of samples.

25. Institutional Tissue Utilization Committee  Formulate criteria for who is eligible to obtain human residual samples at the institution. οFaculty status, IRB approval, ?scientific validity ο?minimum QA requirements ο?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.

26. 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: οthe 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.

27. 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

28. Tissue Utilization Summary VCU Tissue Committee Inova Tissue Committee CTRF Tissue Utilization Group Analyze Samples

29. Database Design/Clinical Info  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

30.  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 Database Design/Data Analysis

31.  Schema (VCU Preliminary)  16 Chips  Test for Variation  Chip-Chip  Labeling  Buffers  Modules (4)  Update – VCU/GMU QA/QC

32. 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

33. QA/QC – GMU Update 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?

34. VCU/MDx quality control: -chip/chip, run/run, fresh/frozen cRNA variation - Human Reference RNA (Stratagene) 200  g total RNA from 10 human cell lines (additional aliquots to be shipped to GMU) Run day#1 Run day#2Total 4 chips/ fresh cRNA 4 chips/ frozen cRNA 16 chips QA/QC – VCU Update

35. Sample Quality: Bioanalyzer (28S/18S ratio) Spectrophotometer (A 260 /A 280 ) 3’/5’ ratio for high abundant transcripts (GAPDH) 3’/5’ ratio for low abundant transcripts (ISGF3A) Quality Control Parameters QA/QC – VCU Update

36. Preliminary analysis Bioanalyzer (28S/18S ratio) 3’/5’ ratio (GAPDH) 3’/5’ ratio (ISGF3A) 0.76 1.83 1.093.68 1.06 9.36 Sample Quality: QA/QC – VCU Update

37. Quality Control Parameters Noise (RawQ) Scaling Factor (SF) Number of Present genes (P/A) Spike controls Linearity (BioB, BioC, BioD, CREX) Signal intensities for housekeeping genes (GAPDH,  -actin) Chip Performance: QA/QC – VCU Update

38. Preliminary analysis Chip Performance: QA/QC – VCU Update Noise (RawQ) CV% < 4% Scaling Factor (SF) CV% < 10% Number of Present genes (P/A) ~ 60% CV% < 2% Signal intensities for housekeeping genes (GAPDH,  - actin) CV% < 7%

39. Preliminary analysis Spike controls Linearity (BioB, BioC, BioD, CREX) Run day#1 Run day#2 QA/QC – VCU Update

40. * Establish Standing Weekly or Biweekly Meeting Dates and Times * Complete the Milestone Updates * Document Discussions and Progress Using Listservs

41.  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 Communication Amongst Members and Focus Groups

42.  Address messages to: listname@VENUS.VCU.EDU  Unsubscribe to the listserv by submitting a message with the words SIGNOFF listname to: 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. LISTSERVS

43.  Old Business  New Business o Presentations by CTRF CaGenomic’s Members at Bioinformatic’s Symposium held on June 12-14, 2002

44.  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 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

45. Monday August 5, 2002 9:30AM