CTRF Leadership Meeting

1. CTRF Leadership Meeting Cancer Genomics and Development of Diagnostic Tools and Therapies June 3, 2002 Institutional Partners V C U G M U I N O V A

2. 5/06/02 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. DRAFT

7. Reminder - Cost Share Form (VCU)

8. Cost Share Expenses • Cost share expenditures not paid from cost share linked ledger 4 account 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)

9. FY 02 Rollover • Rollover process will utilize appropriation adjustments required to be available on July 1, 2002 (Federal fund carry-forward process) • Automated Transaction System (FATS) request must be submitted between June 12 and 14th • Summary of budget status (Carry-Forward Form) • Justification (Transaction brief) • Justification and Carry-Forward Form to be submitted to Dr. Garrett by June 7, 2002

10. Request to Carry Forward Form

11. Justification (Transaction Brief) Reason for year-end balance: The project began late. Funds were not identified until 3 months after the programmatic start date. In addition there was a delay in recruitment of key personnel (ex the director of the tissue acquisition service at VCU did not arrive on site until Dec 2002). Need for carry-forward of these funds: Use of the unexpended funds are essential to continue the project and carry out the programmatic aims of the grant. There are no alternative funds to achieve the specific aims of the grant. In addition, the institutional partners have already made significant matching obligations to this project. How the funds will be used: Funds will be used consistent with the grant proposal

12. FY 03 Allocation • [Submit record of expenditures and matching funds (FY02 Closeout)] • Will need to submit progress indicating milestones achieved in FY02 (in prep - C. Garrett)

13. Website Update • CTRF “News and Updates” page will be added to site • Focus Group roles and responsibility still needed from Focus Group Leaders • URL for site is: www.ctrf-cagenomics.vcu.edu

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

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 • To Contain Inova and VCU Cases • Demo Today after Leadership Meeting

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: • 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.

25. 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.

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: • 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.

27. CTRF Ca Genomics Project Tissue Utilization Group • Project PIs • Tissue Guardians • ?Other Project Leadership • 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. 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

30. Database Design/Data Analysis • GeneX Database (Update) • GMU • VCU • “Terabyte” Database – (Update) • VCU • LabBook (Update - Buck) • VCU

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

32. Normalization and Controls

33. Suggestions for Array Design Among CTRF Members • Spiking: Include the same spiking genes used on the Affy chip, on the C3B and GMU chips • 3’/5’ controls: Include the same genes used on the Affy chip. Can they be added to the GMU chip? • Dynamic Range: This can be implemented on the C3B and GMU chips. • Pin Normalization: This is a statistical routine in the R software package, this can be implemented on the C3B and GMU chip. • 5 Slide Experimental Design

34. 1-Yellow 2-Std 3-Flip 1 2 3 C C C S S C 1 2 3 2/1=Actual Fold change Std = 2’ 3/1=Actual Fold change Flip = 3’ 2’/3’=1 5 Slide Experimental Design

35. 16.55 mm 66.95 mm Microarray Format for the MWG 10K Human Oligo Set Replicate Array 1 KEY Houskeeping Spiking & 3’/5’ Dynamic Range Empty Replicate Array 2

36. CTRF - Promoting Focus Group Activity REMINDER • Establish Standing Weekly or Biweekly Meeting Dates and Times • Complete the Milestone Updates • Document Discussions and Progress Using Listservs

37. Communication Amongst Members and Focus Groups 7 - 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

38. 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.

39. Old Business • New Business • C3B Presentations at BECON2002 Symposium

40. 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) • Any other discoveries • Federal money leveraged • Private research money leveraged • Advancement of technology and economic development in VA

41. Next CTRF Leadership Meeting Monday July, 1 2002 9:30 am

42. Serous Carcinoma