ctrf leadership meeting
DESCRIPTION
Institutional Partners. CTRF Leadership Meeting. Cancer Genomics and Development. of Diagnostic Tools and Therapies. March 3, 2003. 2/3/03. Minutes. Corrections Approval. - PowerPoint PPT PresentationTRANSCRIPT
©2002 VCU
Develop Infrastructure and Intellectual Property that
Enhances the Competitiveness of the Partners for Clinical and
Extramural Funds
Principal ObjectivePrincipal Objective
©2002 VCU
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 ObjectiveResearch Objective
©2002 VCU
ChandhokeGrant
ChristensenFryxell
Jamison
Torr (Central Admin)GinderGarrettBuck
Guiseppe-ElieAbraham
Cooper
Year 1 Year 1 Year 1
$325,000 $582,000 $93,000
Total (3 yrs) Total (3 yrs) Total (3 yrs)
$975,000 $1,734,603 $290,397
Year 2 Year 2 Year 2
$325,000 $578,191 $96,809
Funding for CTRFFunding for CTRF
©2002 VCU
FY02 FundsFY02 Funds
2nd half of the Year 2 CTRF CG Project allocation has been received. Virginia DPB asked VCU OFF BUDGETING & RESOURCE ANALYSIS on 1/21/03 to create the FATS request. VCU did so on 1/22/03 and it was approved by DPB on 1/29/03. State has approved a transfer of $500,000 to VCU for the new CTRF accounts
©2002 VCU
Year 1 Account Balances as Year 1 Account Balances as of 1/29/03 (Old Accounts)of 1/29/03 (Old Accounts)
Account # PI BudgetYTD Exp2-27-03
Account Balance
535282 Central 43,159 43,159 0
535283 Garrett 155,159 155,159 0
535284 * Buck 124,684 124,727 (43)
535285 ** Ginder 93,396 101,475 (8,079)
535286 ** Guiseppi-Eli 150,484 156,887 (6,403)
535287 INOVA 20,802 20,802 0
535288 GMU 325,000 325,000 0
Total: 912,684 927,209 (14,525)
% of Total 100% 101.59% -1.59%
* $43 Hourly payroll / fringe charge for Margaret Barker (H230) has been keyed to the account in error - FA must submit inquiry to remove her from the account. The correct chargecode per her PAF s/ b 5-35384 not 5-35284
** FA needs to submit IDT to transfer overage to Yr 2
Yr 1 Budget 1,000,000$
Yr 1 Expenditures (912,684)
Carryforward to yr 2 87,316$
FY2002 Account Balances as of 2-27-03
©2002 VCU
YR 2 Account Balances as of YR 2 Account Balances as of 2/27/032/27/03
Account # PIYr 2 Original
BudgetYr 1 Carry Forward
Yr 2 Revised Budget
YTD Expenses2-27-03
PendingIDT from Yr 1
Account Balance
535412 Central 43,804 682 44,486 17,322 0 27,164
535413 Garrett 174,974 14,436 189,410 20,810 0 168,600
535499 Buck 131,213 0 131,213 37,719 0 93,494
535417 * Ginder 129,350 0 129,350 12,491 8,079 108,780
535443 * Guiseppi-Eli 98,850 0 98,850 12,696 6,403 79,751
535414 INOVA 96,809 72,198 169,007 0 0 169,007
535415 GMU 325,000 0 325,000 0 0 325,000
Total: 1,000,000 87,316 1,087,316 101,037 14,482 971,797
% of Total 100% 9% 109% 9.29% 1.33% 89.38%
* Yr 1 account # 535285 Ginder535286 Guiseppi-Eli
IDT needed to remove defiicit from Yr 1
FY2002 Account Balances as of 2-27-03
©2002 VCU
Cost Sharing Report YR Cost Sharing Report YR 11
CTRF Grant Acct # PI Budget
Cost Share Requirement
Cost Share Reported
535282 Central 43,839 161,102 235,037
535283 Garrett 169,597 450,881 439,410
535284 Buck 124,684 215,072 236,279
535285 Ginder 93,396 185,216 232,428
535286 Guiseppi-Eli 150,484 304,230 337,628
535287 INOVA- 93,000 345,651 7,284
535288 GMU - V. Chandhoke 325,000 364,536 385,472
$1,000,000 $2,026,688 $1,873,537
©2002 VCU
Cost Sharing Report Yr 2 as Cost Sharing Report Yr 2 as of 1-29-03of 1-29-03
CTRF Grant Acct #
Cost Share Acct #(FRS) PI
Original Cost Share
Requirement (100%)
Revised Cost Share
Requirement (50%)
*Cost Share Expense 1-28-03
(FRS Only)
535412 2-90000 Central 162,899 81,450 59,192
535413 4-12310 Garrett 239,483 119,742 38,884
535499 1-30139 Buck 153,323 76,662 0
535417 4-12320 Ginder 344,786 172,393 0
535443 1-37100 Guiseppi-Eli 215,220 107,610 18,735
535414 - INOVA- 342,365 171,183 0
535415 - GMU- V. Chandhoke 396,592 198,296 0
Total $1,854,668 $927,334 $116,811
Does Not include indirect cost or In-Kind cost sharing.
©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 Cost Share ExpensesExpenses
©2002 VCU
Cost Share UpdateCost Share Update
Meeting with all CTRF Fiscal Administrators took place on 12/12/2002 to review documents of CTRF Cost Sharing Accounts
For in deficit accounts, Fiscal Administrators to do IDTs.
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
©2002 VCU
Website UpdateWebsite 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
©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 ResearchSPIN Research
©2002 VCU
Focus GroupsFocus Groups
Tissue Bank
Clinical & Pathology Laboratory Data
Database Design
Chip Fabrication
QA/QC
Data Analysis
©2002 VCU
Focus Group Leaders
G MU
G e rald in e G ran t ( G M U )S u ha il N as im ( VC U )B a rr ie C o o k ( I n o va)
T issue Bank
L yn ne P en b e rth y (V C U )S u ha il N as im ( VC U )
J a m e s C o op e r ( I n o va)
C linP ath
C u rtis J am is on ( G M U)L yn ne P en b e rth y (V C U )
G re g M ille r (V C U )M ike S he ride n ( I no va)
D B D esign
V ika s C h an d h oke ( G M U )G re g B u ck ( V C U )
D ataA nalysis
A la n C h ris ten s en ( G M U )A n d re a Fe rre ira - G o n zale z (V C U)
S u ha il N as im ( VC U )G e rald ine G ra n t
Q A / LQ C
A ntho ny Gu isepp i-E lieA lan Christensen
Ch ip Fabrication
VCU I nova
Focus Group LeadersFocus Group Leaders
©2002 VCU
VCU Tissue BankVCU Tissue Bank
Breast 41
Bone Marrow 128
Ovary 13
Head & Neck 3
Lymphoma 7
Brain 3
Tissue Type Specimen Count
©2002 VCU
INOVA – CTRF – Tissue INOVA – CTRF – Tissue BankBank
Jean Donovan, RN has been hired at INOVA as new study coordinator
Colleen Gilmore, RN has also been hired as part-time coordinator
Training will begin next week for both coordinators
©2002 VCU
Tissue Type Specimen Count
INOVA Tissue BankINOVA Tissue Bank
Brain 2
Breast 2
INOVA has begun accessioning tissue samples and obtaining consents.
©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 Tissue Acquisition DatabaseDatabase
©2002 VCU
ICD9_Code Description
Patient Total
Patient w/ one or more
Grade 1/2 Samples
Patients w/ one or more
Grade 3 Samples
Patient w/one or
more Grade N/A
Patients w/one or
more Lymph Node
Dissected Samples
Patients w/ one or more Lymph Node
Positive Samples
Patients w/ one or more
Estrogen Recep
Positive Samples
Patients w/ one or more
Her2Neu Positive Samples
Patients w/ one or
more Stage I/II
Samples
85203 Adenocarcinoma Lobular 2 1 0 1 2 0 1 0 2
85223
Carcinoma Duct Infiltrating &
Lobular 2 0 1 1 2 2 1 1 0
85213
Carcinoma Ductular
Infiltrating 22 11 11 0 22 12 7 5 16
89803 Carcinosarcoma NOS 2 0 1 1 2 0 0 0 2
Breast – Diagnosis Breast – Diagnosis DistributionDistribution
©2002 VCU
ICD9_Code Description
Patient
Total
Patient w/
one or more
Grade 1/2
Samples
Patient w/
one or more
Grade 3
Samples
Patient
w/one or
more Grade
N/A
Patient w/
one or more
Path Stage
I/II Samples
Patient w/
one or more
Path Stage
III/IV
Samples
Patient w/
one or more
Path Invasion
Samples
84603 Adenocarcinoma Papillary Serous 3 1 1 1 1 2 0
84413 Adenocarcinoma Serous NOS 1 0 1 0 0 1 0
84613 Carcinoma Papillary Serous Surfa 3 1 2 0 1 2 0
84423 Cystadenoma Serous Borderline Ma 1 0 0 1 0 1 0
85901 Gonadal Stromal Tumor 1 0 0 1 0 0 0
86201 Granulosa Cell Tumor NOS 1 0 0 1 1 0 0
Ovary – Diagnosis Ovary – Diagnosis DistributionDistribution
©2002 VCU
Hematopoietic Neoplasia – Hematopoietic Neoplasia – Diagnosis DistributionDiagnosis Distribution
Description
Patient
Total
Patient w/one or
more Diagnostic
Samples
Patient w/one or
more Remission
Samples
Patient w/one or
more Remiss
Post BMT
Samples
Patient w/one
or more
Relapseon
Samples
Patient w/one
or more Staging
Samples
Patient w/one
or more
Unknown
Samples
Hodgkin's Disease 2 0 0 1 0 0 1
Lymphoid Leukemia, acute 3 2 2 0 1 0 0
Lymphoid Leukemia, chronic 5 4 1 0 0 0 2
Monocytic Leukemia 1 0 1 0 0 0 0
Monocytic Leukemia, acute 2 2 2 0 0 0 0
Multiple Myeloma 6 4 1 0 0 0 0
Myelodysplastic syndrome 3 3 1 0 0 0 2
Myeloid leukemia, acute 18 6 10 1 5 0 0
Myeloid leukemia, chronic 9 3 6 0 0 0 2Neoplasm of uncert. Behavior of other lymphatic & hemat. 1 0 0 0 0 0 0
Non-Hodgkin's Lymphoma 1 0 0 1 0 0 0
Other 14 0 0 0 0 0 0Other Lymphomas 11 0 0 1 0 9 1
Study IDTissue IDSample ID
Sub-sample ID
Study IDSSN
Clinical Data ModelClinical Data Model (VCU) - Primary: Data Collection
Secondary: Queries, Data Reduction, Anonymization
Tertiary: Analysis & Hypothesis Testing
AFFYTISSBK & 1o CLINICAL & Consent
CERNER
PathShadw
REGISTRY CLAIMS
Clinical Data Repository
SPOTTED
Gene Expressio
n
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 dataSpot data
Experimental(Metadata)
Reg Shadw
GeneX
Clinical Risk Factors
Treatments
Outcomes
Histopath Risk Factors
Path Dx
Clin Lab
ExpandedGeneX
Table: Consent
Info
Tables: Demogrph
s Risk Factrs
Nutirtion Comorbidt
y 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
©2002 VCU
GMU Informatics GMU Informatics UpdateUpdate
– 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.
©2002 VCU
Results (I)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.
©2002 VCU
Results (II)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).
©2002 VCU
Dr. Nasim and Dr. Dr. Nasim and Dr. GrantGrant
Tissue Devitalization
•Awaiting specimen of sufficient size to create multiple samples over time
Alias Grade Mitotic Score Tumor Stage Inflamm InSitu ER PR Prolif Lymph Node Her2/Neu 28S/18S A260/A280 GAPDH 3'/5' -actin 3'/5'
BR- 20 1 1 T1 I No Yes Yes No Low No - 1.6 2.2 1.34 1.75BR-16 2 1 T1 I - Yes Yes No Low No No 1.6 2.1 1.35 1.65BR-17 2 1 T1 I No Yes Yes Yes Low No No 1.3 2.1 1.11 1.33BR-15 2 1 T1 I No No Yes No Low No No 1.7 2.2 0.88 1.34BR-01 3 3 T2 IIA No No No No High No No 1.2 2.3 1.17 2.01BR-01' 3 3 T2 IIA No No No No High No No 1.6 2.1 0.91 1.23BR-11 3 3 T2 IIB No Yes No No High No No 1.8 2.2 1.40 1.14BR-03 3 2 T2 IIB No Yes Yes Yes Low No No 1.6 2.4 1.09 1.76BR-04 3 3 T2 IIB No No No No Low No No 1.5 2.1 0.94 1.40BR-21 2 3 T2 IIA No Yes Yes Yes High Yes No 1.5 2.2 0.92 1.22BR-06 3 3 T3 IIIA No Yes Yes No Low Yes No 1.8 2.2 2.87 3.23BR-10 3 3 T4 IIIB Yes No No No High Yes No 1.8 2.1 1.11 0.92BR-12 2 1 T1 I No Yes Yes Yes High Yes Yes 1.4 2.2 1.00 1.06BR-09 3 2 T2 IIIC No No Yes No High Yes Yes 1.8 2.1 2.19 2.48BR-19 3 3 T2 IIIA No Yes Yes Yes High Yes Yes 1.4 2.2 1.23 1.79BR-13 3 2 T2 IIA No Yes No No High Yes Yes 1.4 2.1 1.43 1.10
Alias Grade Category Histology Tumor Stage Lymph Node Metast 28S/18S A260/A280 GAPDH 3'/5' -actin 3'/5'OV-02 - sex cord/stromal Sertoli-Leydig Benign - - - 1.5 2.1 0.81 1.35OV-TB - epithelial Serous T1a IIIC N1 M0 1.9 2.2 1.20 1.76OV-04 2 epithelial Mixed Serous Endometrioid T2b IIB N0 M0 1.4 2.2 1.03 1.39OV-08 3 epithelial Serous T2b IIB N0 M0 1.6 2.2 1.26 1.59OV-05 3 epithelial Serous T3 IV N0 M0 2.2 2.3 1.00 1.57OV-07 - epithelial Serous T3 IIIC N1 M0 1.1 2.1 1.14 2.16OV-06 2 epithelial Serous T3b IIIB N0 M0 1.7 2.1 1.26 1.42OV-01 3 epithelial Mixed Serous Endometrioid T2b IV N0 M1 1.7 2.1 1.03 1.57OV-03 3 epithelial Serous T3 VI N0 M1 1.7 2.1 1.74 4.64
1098 genes>4-fold change
Sex
Cho
rd
Ovary Breast
OV
-02
OV
-04
OV
-TB
OV
-03
OV
-01
OV
-08
OV
-07
OV
-05
OV
-06
BR
-01’
BR
-01
BR
-10
BR
-03
BR
-04
BR
-09
BR
-12
BR
-19
BR
-11
BR
-13
BR
-06
BR
-21
BR
-15
BR
-20
BR
-16
BR
-17
1098 genes>4-fold change
Sex
Cho
rd
Ovary BreastOvary Breast
OV
-02
OV
-04
OV
-TB
OV
-03
OV
-01
OV
-08
OV
-07
OV
-05
OV
-06
BR
-01’
BR
-01
BR
-10
BR
-03
BR
-04
BR
-09
BR
-12
BR
-19
BR
-11
BR
-13
BR
-06
BR
-21
BR
-15
BR
-20
BR
-16
BR
-17
Gene Expression Data Analysis of Breast & Gene Expression Data Analysis of Breast & Ovary TumorsOvary Tumors
©2002 VCU
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.
Gene Expression Data Gene Expression Data Analysis of Breast & Ovary Analysis of Breast & Ovary
Tumors SummaryTumors Summary
©2002 VCU
Progress ReportProgress Report
• Completed Printing ~200 C3B10k microarrays.• Hybridized Arabidopsis control oligos to 1 array from each
of the four 50 slide batches to confirm viability. • Begun preliminary variability studies using Stratagene
RNA, and RNA from human glioma cell lines.• Presented poster “Surface Chemistries and Blocking
Strategies” at the annual AAAS meeting in Denver Feb 14-16.
• Grant proposal for $200,000 for 2 years in preparation for submission to the Brain Tumor Society.
• Cancer Treatment Research Fund identified for possible funding source, pregrant preparation in progress.
• Exchange student Derk Bemeleit from the University of Bremen in Germany has joined the C3B lab to work on gene expression in glioma cell lines.
©2002 VCU
Establish Standing Weekly or Biweekly Meeting Dates
and Times
Complete the Milestone Updates
Document Discussions and Progress Using
Listservs
CTRF – Promoting Focus CTRF – Promoting Focus Group ActivityGroup Activity
©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 Communication Amongst Members and Focus GroupsMembers and Focus Groups
©2002 VCU
CTRF - Specific CTRF - Specific ReportablesReportables
- - Reminder - -- 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