CTRF Leadership Meeting Cancer Genomics and Development of Diagnostic Tools and Therapies January 13, 2002 Institutional Partners V C U G M U I N O V A
12/09/02 Minutes Corrections Approval
Develop Infrastructure and Intellectual Property that Enhances the Competitiveness of the Partners for Clinical and Extramural Funds Principal 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 Funds • State has approved a transfer of $500,000 to VCU for the new CTRF accounts • Money has been allocated by VCU Grants and Contracts into the new CTRF Accounts
CTRF YR02 Initial Budget Allocation * Year 2 Modified Budget distribution based on State allocation of $500,000 as of 11/2002
CTRF YR02 Current Budget Status * Year 2 Modified Budget distribution based on State allocation of $500,000 as of 11/2002
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)
Cost Share Update • Meeting with all CTRF Fiscal Administrators took place on 12/12/2002 to review documents of CTRF Cost Sharing Accounts • Cost Sharing will be taken out of Ledger 1 Accounts and PAFs will be used to document Salaries
Website Update • Website still incomplete; information regarding focus group activities is needed www.ctrf-cagenomics.vcu.edu
SPIN Research • 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
Focus Groups Tissue Bank Clinical & Pathology Laboratory Data Database Design QA/QC Data Analysis Chip Fabrication
Annual Report • Was submitted on Friday, January 27th to Judy Heiman
Annual Report Highlights • QA/QC Studies • VCU MDX, NARF (Previously presented) • GMU (Previously presented) • VCU CB3 • Preliminary Evaluation of Breast and Ovarian Cancer Samples • Deliverables (Publications, Presentations, Grant Applications)
Primary array Replicate array Key: Dynamic Range 3’/ 5’ and Affy Spiking controls All other colors are housekeeping genes Design and Control Gene Layout for the C3B 10K Microarray
C3B 10K Array process Variability Study using the Stratagene Universal Human Reference mRNA Will use the Stratagene Human Reference mRNA (Product #: 740000-41) (lot number 1000207 can be obtained from A. Christensen or A. Ferreira-Gonzalez)
C3B 10K Microarray:Cell Line Studies • Effect of organo-platinum therapeutics (Cis-platin) on gliblastoma cell lines • To survey the changes in gene expression due to treatment of glioblastoma cell lines with Platinum containing chemotherapeutics H N C l 3 P t C l H N 3 Cisplatin
Gene Expression Data Analysis of Breast & Ovary Tumors Summary From the previous analysis we concluded that a good correlation between the histological classification and gene expression clustering could be accomplished among the cancer cases so far analyzed. Further associations between gene expression patterns and more complete histopathological and clinical data are now being analyzed intended to make gene expression profiles of tumor tissues an early predictive tool of good or bad outcome for cancer patients.
INOVA – CTRF – Tissue Bank • INOVA has obtained first tissue sample (brain specimen) • IRB has approved tissue acquisition system for INOVA • Dr. Dorriane Watts to replace Marianne Smith as Interim Director of Research • Renee Brenner to be collecting specimens for INOVA currently; a new permanent coordinator to be hired
Tissue Acquisition Database • Access Database • Computer has been installed at INOVA • Database has been installed on machine at VCU • INOVA connected to database at VCU using PC Anywhere (8-20-02) • Update of Database for Histopathologic parameters of existing cases needed - Completed
Diagnosis Distribution - Hematopoietic Neoplasia **Data incomplete for this tissue type
Clinical Data Model (VCU) - Primary: Data Collection AFFY Study ID Tissue ID Sample ID Sub-sample ID TISSBK & 1oCLINICAL & Consent Study ID SSN CERNER REGISTRY CLAIMS PathShadw MRN SSN Path Accsn MRN SSN ACCSN SEQ MRN SSN PAN Reg Shadw SPOTTED Histopath Risk Factors Path Dx Clin Lab Study ID Lab ID Tissue ID Run ID Clinical Risk Factors Treatments Outcomes Secondary: Queries, Data Reduction, Anonymization GeneX CEL file data Spot data Experimental (Metadata) Clinical Data Repository Table: Consent Info Tables: Extract Info StorageInfo Usage Info etc Tables: Histopath parameters Path Dxs SNOMED Text Repts Tables: Demogrphs Risk Factrs Nutirtion Comorbidty etc Tables: Tumor info Treatment Follow-up etc Tables: Surg Tx Medical Tx Radiatin Tx other dxs Tertiary: Analysis & Hypothesis Testing Gene Expression Non-genetic predictors Treatments Outcomes Expanded GeneX
GMU Informatics Update • Create or Identify existing databases into which expression microarray data can be stored in electronic format in real time at this juncture. • 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.
CTRF CA GENOMICS TISSUE UTILIZATION - PLAN QA Program
Results (I) • By using TRIZOL 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 TRIZOL with the RNeasy cleanup protocol, we obtained cDNA molecules of greater size, with a max. peak at ~1,500 bp.
Results (II) • By usingthe RNeasyRNA 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).
Devitalization of Tissue Dr. Nasim and Dr. Grant
Tissue Devitalization • Breast samples collected VCU • Tissue to be snap frozen over a time series (15, 30, 60, 120 minutes) • Sections cut and placed directly in TRIZOL • Problem – Different blocks of tissue differed significantly in amount and viability of cancer cells (Pathologist review) • Outcome – repeat study with new cancer specimen
CTRF – Promoting Focus Group Activity • Establish Standing Weekly or Biweekly Meeting Dates and Times • Document Discussions and Progress Using Listservs Complete the Milestone Updates
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
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
Old Business • New Business
Next Leadership Meeting Will be held: Monday, February 3, 2003 at 9:00am