ctrf leadership meeting

CTRF Leadership Meeting

Institutional Partners

March 3, 2003

©2002 VCU

2/3/03

Minutes

Corrections

Approval

©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

Reminder Cost Share Form Reminder Cost Share Form (VCU)(VCU)

©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


Estrogen Recep

Positive Samples


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

CTRF CA GENOMICS TISSUE CTRF CA GENOMICS TISSUE UTILIZATION - PLANUTILIZATION - PLAN

©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

Publications & PresentationsPublications & Presentations

Publications & Presentations Con’tPublications & Presentations Con’t

New Applications IdentifiedNew Applications Identified

Next Leadership Meeting

Will be held:

Monday, April 7, 2003 at 9:30am

Mucinous Carcinoma (of the breast )

ctrf leadership meeting

Documents