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Moving Omics to Clinics:
BioSpecimen Science Driving
Sample-Centered Precision Medicine
Michael H. A. Roehrl, M.D., Ph.D.
Director, UHN Program in BioSpecimen Sciences
Investigator, Ontario Cancer Institute (OCI)
Member, Ontario Institute for Cancer Research (OICR)
Associate Professor of Pathology and Laboratory Medicine
University of Toronto
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
UHN BioSpecimen Sciences – Overview
• BioBanking
Biospecimen Collection
Ultra-Rapid BioBanking
• Database Integration
Clinical Records
Molecular Signatures
Data-Rich Specimen Annotation
• Systems-Level Specimen Characterization
Next Gen Sequencing
Proteomics
Metabolomics
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
UHN BioSpecimen Sciences – Workflow
BioSpecimen
Sciences
Dt
OR or clinic
Accession
Label
Dissect
Aliquot
Annotate
Storage/
Retrieval
IT Database Cloud
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
UHN BioSpecimen Sciences
Diagnostics
Biospecimens
Banking
Informed consent process
(>95% consent rate)
Bioinformatics and
Database Structures
Biomedical Research and Clinical Trials
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
Consenting Patients for Research Specimen Collection
Patient Clinic Visit
Patient charts
screened for consent
by UHN BSP
Research
Coordinators
Patient PreAdmission Visit
Surgery Waiting
Area
Patient charts
screened for consent
by UHN Biobank
Patho logy Assistants
Patients approached
for consent by
UHN BSP
Research
Coordinator
Patient Surgery
Post-operative
Patients
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
Consenting Patients for Research Specimen Collection
Site
Agreed
Refused
Undecided
Withdrew
Thyroid n=83
80 (96.4%)
3 (3.6%)
0
0
Pancreas n=120
117 (97.5%)
2 (1.7%)
1 (0.8%)
0
Pop-Cure n=2
2 (100%)
0
0
0
Neuroendocrine n=5
5 (100%)
0
0
0
Gynecological n=36
30 (83.3%)
3 (8.3%)
2 (5.6%)
1 (2.8%)
Total n=246 (100%)
234 (95.1%)
8 (3.3%)
3 (1.2%)
1 (0.4%)
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
High Volume Frozen Tissue Sample Accrual
Annual Number of Frozen Tissue Samples
14000
Total: >92,000
12000
Male: 49%
Female: 51%
10000
8000
6000
4000
2000
0
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Year of Collection
(projected)
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
Th
yro
Br id
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Kid st
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Or Lun
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Pa avity
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Pr eas
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S
S t o k in
ma
Ad c h
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Bla nal
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er
H
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a
La oph rt
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ag
Sm Inte us
s
all
Int tine
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e
Ly Lar
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Me h No x
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sti e
nu
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Pa Ne
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Pit rath k
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Sa ary G id
liva
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So Glan
ft T
d
iss
ue
Sp
lee
Te n
s
Th tis
ym
Va us
sc
ula
r
GY
N
Number of Tissue Samples
Broad Disease Site Representation
16000
14000
10000
8000
6000
4000
2000
0
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
UHN BioSpecimen Sciences: Research Samples 2012
Fresh Frozen Tissue
Blood Samples
3452 unique patients
1077 unique patients
12502 LN-frozen samples
6462 LN-frozen samples
9489 paraffin blocks
Other Body Fluids
Autopsies
57 unique patients
50 unique patients (3 rapid)
116 fresh samples
162 LN-frozen samples
570 LN-frozen vials
OCI/PMH Research Autopsy Grant
(PI: Roehrl)
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
The Current “Umbrella Trial” Design
Lung Cancer
Breast Cancer
Randomized trial and error by organ site
Colorectal Cancer
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
Targeting TKI Resistance in Cancer (Using MAPK as an Example)
Targeting other
RTKs of same
family
Targeting
other RTKs
IRS
PI3K
TSC2
AKT
PTEN
Shc
Sos
Grb2
Ras
TSC1
Targeting
multiple
oncogenic
pathways
(horizontal
blockade)
RHEB
mTOR
S6K
Raf
MEK
1/2
Targeting
multiple
nodes of the
same
oncogenic
pathway
(vertical
blockade)
ERK
1/2
4E-BP
Transcription
Translation
Growth, Proliferation, Metastasis, Survival
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
Molecularly Driven Trials
Molecular Trials are now
Sample-Centered
Clinical trial: Site-independent,
aberration-specific
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
UHN BioSpecimen Sciences – IT Development
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
Research Specimen IT: Site-Derivative Data Model
Global Site-Derivative Model
Sample Site #1
(e.g., tumor)
Sample #1 (LN frozen)
Sample #2 (paraffin)
Sample #N
Sample Site #2
(e.g., adjacent adenoma)
Patient Event #1
(e.g., colectomy)
Site (e.g., colon)
Derivative #1 (DNA)
Derivative #2 (RNA)
Derivative #1 (HE slide)
Derivative #2 (IHC slide)
Individual
pathological header
diagnoses
Sample Site #3
(e.g., ulcerative colitis/IBD)
Pathology full text
report for event #1
…
Sample Site #N
(e.g., “normal colon”)
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
UHN BioSpecimen Sciences – Data Network
UHN EPR
Patient
Demographic
Info
CoPath
UHN Pathology
Synoptic
Reports
Caisis
Clinical Annotations
Clinical Trials
UHN Advanced
Clinical
Documentation
caTissueSuite
Specimen
Management
SAP
Data Federation
and
Reporting
UHN
BioBank
eCare
DADOS
MosaiQ
Clinical Annotation
Research
Community
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
The Integrated Specimen Set
Before Surgery
During Surgery
After Surgery
Lesional tissue
Whole blood
Whole blood
Normal tissue
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
The Integrated Specimen Set
Before Surgery
During Surgery
After Surgery
Lesional tissue
Whole blood
Whole blood
Normal tissue
“The Perfect Quartet”
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
The Integrated Specimen Set Plus
Before Surgery
During Surgery
After Surgery
Follow-up
Whole blood
Serum
Plasma
Buffy coat
Urine
Saliva
Ascites
Other
Lesional tissue
Whole blood
Serum
Plasma
Buffy coat
Urine
Saliva
Ascites
Other
Biopsy
Whole blood
Serum
Plasma
Buffy coat
Urine
Saliva
Ascites
Other
Normal tissue
Longitudinal Specimen Representation of Every Patient
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
The Integrated Specimen Set Plus
Patient Event
Lab Information System
Clinical Labs
Clinical Results
(Electronic Patient Record)
Initial Visit
Biopsy
Resection
Chemo-RT
Integrated
Aliquoter
Research BioBank
Follow-up
Recurrence
Time
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
Pioneering Ultra-Rapid BioBanking
0 min
Consultation
Ultra-Rapid BioBanking
1 min
<5 min
5 min
10 min
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
UHN Rapid Research Autopsy Program
0h
Melanoma
Research Autopsy
1-2 h
Comprehensive collection of:
• Primary site
• Metastases
3-5 h
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
Molecular Specimen Characterization
• Digital image scanning
• Tissue microarray construction
• Immunohistochemical analysis
• Laser microdissection
• Genome sequencing and large gene panel sequencing (e.g., 535 gene cancer panel)
• Proteome and metabolome characterization of specimens
• Systems-based data integration of clinical patient data with omic-level specimen
profiles
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
Stringent Biospecimen Quality Requirements
Formalin-fixed, paraffin-embedded (FFPE)
Tissue in “OCT”
(optimal cutting temperature; glycols/resins)
Genomics
Transcriptomics
Proteomics
Tissue in some sort of “stabilizer”
(fixatives and/or degradation inhibitors;
e.g., RNAlater is ammonium sulfate)
Proteomics with PTMs
Tissue at low temperature (LN)
Lipidomics/Glycomics
Ultra-rapid procurement and low temperature
Metabolomics
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
Stringent Biospecimen Quality Requirements
Formalin-fixed, paraffin-embedded (FFPE)
Tissue in “OCT”
(optimal cutting temperature; glycols/resins)
Genomics
Transcriptomics
Proteomics
Tissue in some sort of “stabilizer”
(fixatives and/or degradation inhibitors;
e.g., RNAlater is ammonium sulfate)
Proteomics with PTMs
Tissue at low temperature (LN)
Lipidomics/Glycomics
Ultra-rapid procurement and low temperature
Metabolomics
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
Stringent Biospecimen Quality Requirements
Formalin-fixed, paraffin-embedded (FFPE)
Tissue in “OCT”
(optimal cutting temperature; glycols/resins)
Genomics
Transcriptomics
Proteomics
Tissue in some sort of “stabilizer”
(fixatives and/or degradation inhibitors;
e.g., RNAlater is ammonium sulfate)
Proteomics with PTMs
Tissue at low temperature (LN)
Lipidomics/Glycomics
Ultra-rapid procurement and low temperature
Metabolomics
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
Solving Tissue Heterogeneity: Laser Capture Microdissection and Next Gen Sequencing
Case 2(BSP# 66189)
Case 3(BSP# 69598)
Roehrl MHA et al.
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
PCSI_0047_Pa_P
Bulk Sample Exome
KRAS
C:80
T:13 (14%)
LCM WGS (2 lanes)
KRAS
C:10
T:9 (47%)
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
The Need for Highest Quality Biospecimens: Tissue Proteomics
• New proteomic biomarkers of carcinomas
• Importance and complexity of the proteome in the pathophysiology of human cancer
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
The Need for Highest Quality Biospecimens: Metabolomics
• Quantitative NMR spectroscopy of cancer metabolites
• Discovery of altered metabolite patterns
• Development of statistical models that separate normal from diseased tissue
• Glycolytic and fatty acid pathways altered
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
BioSpecimen Science: Integrating Personalized Cancer
Genomes and Functional Characterization
Exome/WG sequence
Personalized database representing
all patient-specific aberrations
Personalized functional characterization
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)
BioSpecimen Science: Training Molecular Physicians of the Future
Data Source
Technology
Data Analysis
DNA
RNA
Data Interpretation
Proteins
Medical Action
Metabolites
PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Michael H. A. Roehrl)