1. CTRF Leadership Meeting Institutional Partners April 7, 2003

2. © 2002 VCU 3/3/03 Minutes Corrections Approval

3. © 2002 VCU Develop Infrastructure and Intellectual Property that Enhances the Competitiveness of the Partners for Clinical and Extramural Funds Principal Objective

4. © 2002 VCU  Evaluate gene expression (and genetic changes) in human brain, ovarian, breast and hematopoetic cancers and lung, colo-rectal, head and neck, and biliary tract 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. © 2002 VCU Funding for CTRF

6. © 2002 VCU Year 1 Account Balances as of 4/3/03 (Old Accounts)

7. © 2002 VCU YR 2 Account Balances as of 4/1/03

8. © 2002 VCU Cost Sharing Report as of 4/1/03

9. © 2002 VCU  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) Cost Share Expenses

10. © 2002 VCU Cost Share Update  Cost Sharing will be taken out of Ledger 1 Accounts and PAFs will be used to document Salaries  Cost sharing will be updated on a quarterly span  Documentation of Cost Share at VCU to be forwarded to Michael Newsome (manewsom@vcu.edu)

11. © 2002 VCU Reminder Cost Share Form (VCU)

12. © 2002 VCU Website Update  Website has been updated in some areas  Information is still needed regarding various focus group activities  The CTRF Website is best viewed in Internet Explorer 5.0v or better

13. © 2002 VCU  Jo Ann Breaux receiving daily notices of grant opportunities  Compiling weekly document of relevant findings  Monthly SMART documents currently on the CTRF website Training is available: http://www.InfoEd.org/default.stm SPIN Research

14. © 2002 VCU Focus Groups Tissue Bank Clinical & Pathology Laboratory Data Database Design Chip Fabrication QA/QC Data Analysis

15. © 2002 VCU Focus Group Leaders

16. © 2002 VCU VCU Tissue Bank Tissue Type Specimen Count

17. © 2002 VCU Breast – Diagnosis Distribution

18. © 2002 VCU Ovary – Diagnosis Distribution

19. © 2002 VCU Hematopoietic Neoplasia – Diagnosis Distribution

20. © 2002 VCU INOVA – CTRF – Tissue Bank  Jean Donovan being transitioned to full time CTRF Cancer Research Coordinator  In-Service Meetings are schedule with Cancer Committee, Pathology Department, and Surgical Department to inform them about CTRF study  Computer for data entry have been acquired; awaiting dedicated phone line.

21. © 2002 VCU Tissue Type Specimen Count INOVA Tissue Bank Brain4 Breast4  INOVA has begun accessioning tissue samples and obtaining consents.

22. © 2002 VCU  Access Database  VCU linked by LAN for several users  Computer at INOVA to be upgraded and VPN software to be installed Tissue Acquisition Database

23. FactG_ID Consent_ID FactG_Date GP1 GP2 GP3 GP4 GP5 GP6 GP7 GS1 GS2 GS3 Questions_FactG Tissue_type_ID Tissue_type_Desc Quest_Form_ID Tissue_Type Disease_ID Tissue_type_ID Disease_Tissue Disease_ID Disease_Desc Disease Tissue_Bank_Case_Num Sample_Num Original_Sample_Size Current_Sample_Size Process_type_ID Tumor_Loc_ID Institution Storage_Loc_Freezer Storage_Loc_Box Storage_Loc_Slot Frozen_Dt_Tm AP_Specimen_Num Diagnosis Exhausted Cut_in Inadequate_Tumor Tissue_Bank_Sample Tissue_Bank_Case_Num Sample_Num Subsample_Num Alias Dimension1 Dimension2 DimensionCalc CubicSize SectionsCount Process_type_ID Process_Dt PctTumor CharChange Institution_ID Storage_Loc_Freezer Storage_Loc_Box Storage_Loc_Slot Storage_Loc_Slide Extracted Tissue_Bank_Subsample Extraction_ID Alias Tissue_Bank_Case_Num Sample_Num Subsample_Num Date SpectRatioAC SpectRatioAB SpectConc SpectYield FluoPctDNA BioanlyzRation BioanlyzConc BioanlyzPctrRNA RNA Template CRNA260_280 cRNAYieldmicrog cRNAYielDist cDNASizeDist Removed_Person Institution_ID Protocol Removed_Dt_Tm Extracted_Sample_Size Returned_Dt_Tm Percent_Tumor Background_Avg Noise_RawQ Scale_Factor TGT_Value GAPDH B_actin SrRNA18 SrRNA28 Tissue_Bank_Extraction Consent_ID Patient_ID Consent_Dt_Tm Tissue_type_ID Patient_Consent Patient_ID Medical_Record_Nu Institution_ID Patient_Alias_ID Patient_Alias Institution_ID Institution_Desc Institution Histopath_Ovarian_ID Tissue_Bank_Case_Num Gross Position Size Histo_Category_ID Histo_Clasification_ID Histo_SubClassification_ID Grade Invasion WHO_Code Tumor Lymph_Node Metastasis Pathological_Stage Histopath_Ovarian Tissue_Bank_Case_Num Patient_Alias_ID Surgeon_ID Surgery_Dt_Tm Incision_Dt_Tm Extirpation_Dt_Tm Transport_Meth_ID Tissue_type_ID HP_Initial_Diagnosis AP_Accession Path_Report_Control Diagnosis Start_Anesth_Dt_Tm Consent_Status AP_Accession_Unformatt ed ICD9_Code Verify Tissue_Available Surg_Path_Pers Comment Cut_in Tissue_Bank_Case State_ID Abbreviation State/Possession State_Abbrev Country_ID Abbreviation Country Country Abbrev Gender_ID Gender_Desc Gender Race_ID Race_Desc Race Patient_ID Name_Last Name_First Name_Middle Name_Full_Formatted Name_Last_Center Name_First_Center Name_Middle_Center Street1 Street2 City State_ID Zip Code Country_ID Area Code Phone Number Birth_Dt_Tm Gender_ID Race_ID Social_Security_Number Interview Deceased Deceased_Date Interview_type Patient

24. © 2002 VCU Total Tissue by Disease

25. © 2002 VCU HistoPath Done

26. © 2002 VCU Questionnaires Done

27. Study ID Tissue ID Sample ID Sub-sample ID Study ID SSN Clinical Data Model Clinical Data Model (VCU) - Primary: Data Collection Secondary: Queries, Data Reduction Tertiary: Analysis & Hypothesis Testing AFFY TISSBK & 1 o CLINICAL & Consent CERNER PathShadw REGISTRY CLAIMS Clinical Data Repository SPOTTED Gene Expression Non-genetic predictors Treatments Outcomes MRN SSN ACCSN SEQ MRN SSN PAN MRN SSN Path Accsn Study ID Lab ID Tissue ID Run ID CEL file data Spot data Experimental (Metadata) Reg Shadw GeneX Clinical Risk Factors Treatments Outcomes Histopath Risk Factors Path Dx Clin Lab Analysis Database Table: Consent Info Tables: Demogrphs Risk Factrs Nutirtion Comorbidty etc Tables: Extract Info StorageInfo Usage Info etc Tables: Histopath parameters Path Dxs SNOMED Text Repts Tables: Tumor info Treatment Follow-up etc Tables: Surg Tx Medical Tx Radiatin Tx other dxs

28. © 2002 VCU GMU Informatics Update –Identified GeneX as candidate microarray database. –Worked with GeneX developers and UVA to modify GeneX to accept both cDNA and Affymetrix gene expression data –Instantiated new version of GeneX –Defined new LIMS schema for data management Create or Identify existing databases into which clinical, laboratory, tissue bank information, and expression microarray can be stored in electronic format in real time at this juncture. –Examined several available clinical databases and found none to be sufficient in terms of performance and flexibility. –Used CGO as starting basis to generate new clinical schema. –Currently implementing clinical databases. Create ODBC links between separate databases containing clinical, laboratory, and tissue bank data. –In progress. Create or Identify existing databases into which expression microarray data can be stored in electronic format in real time at this juncture.

29. © 2002 VCU CTRF CA GENOMICS TISSUE UTILIZATION - PLAN

30. © 2002 VCU Results (I)  By using T RIZOL we obtained undegraded RNA (28S/18S >1.5) but the cDNA synthesis was inhibited (accumulation of short, ~50 bp, molecules).  By cleaning up the RNA isolated using T RIZOL with the RNeasy cleanup protocol, we obtained cDNA molecules of greater size, with a max. peak at ~1,500 bp.

31. © 2002 VCU Results (II)  By using the RNeasy RNA isolation protocol from breast tissue sections, we obtained total RNA with 28S/18S ratios << 1.5, and the cDNA molecules were shorter than expected (max. peak at ~500 bp).  Therefore, we decided to isolate the RNA using TRIZOL followed by the RNeasy cleanup protocol, to ensure cDNA molecules of greater size, (max. peak at ~1,500 bp).

32. © 2002 VCU Dr. Nasim and Dr. Grant Tissue Devitalization Awaiting specimen of sufficient size to create multiple samples over time

33. © 2002 VCU Gene Expression

34. Gene Expression Data Analysis of Breast & Ovary Tumors

35. © 2002 VCU Cases Processed for Participating Labs

36. © 2002 VCU  Establish Standing Weekly or Biweekly Meeting Dates and Times  Complete the Milestone Updates  Document Discussions and Progress Using Listservs CTRF – Promoting Focus Group Activity

37. © 2002 VCU  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

38. © 2002 VCU CTRF - Specific Reportables - - Reminder - -  Intellectual property reporting - licenses, patents, etc  Publications  New applications  Federal money leveraged  Private research money leveraged  Advancement of technology and economic development in VA

39. © 2002 VCU New Grant Applications $200,000 - Genomic Classification of Primary Brain Tumors and Development of Diagnostic Biochips (Anthony Guiseppi-Elie, Sc.D) 01/01/04-12/31/07 - $2,000,000 - Clinical and Molecular Measurements Predicting Optimal Breast Cancer Therapies – (Peter O’Connell, Ph.D)

40. © 2002 VCU  Old Business  New Business

41. Next Leadership Meeting Will be held: Monday, May 5, 2003 at 9:30am