Understanding SNPs and Cancer

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Erin MillikenL. Michelle Bennett
Understanding Genome-Wide Profiling of Cancer
Donna Kerrigan, M.S. E. Milliken, Ph.D. L.M.
Bennett, Ph.D.
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Single Gene Tests A Locally Focused Search
Continent
Country
U.S. State
World
Chemical bases
Chromosome
Genome
Gene
A
G
T
C
Cell
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Genome-Wide Profiling A Globally Focused Search
Continent
Country
U.S. State
World
Chemical bases
Chromosome
Genome
Gene
A
G
T
C
Cell
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Starts with Proper Collection and Storage
Informed consent
Carefully refreeze
Carefully retrieve and analyze
Store
Add unique identifier
Biopsy sample
The specimen is biologically viable
Post-acquisition
Pre-acquisition
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Genome-Wide Profiling Many Ways
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Genome-Wide Profiling Comparative Genomic
Hybridization
equal binding of labeled normal and tumor probes
more binding of labeled tumor probesgain of
tumor DNA
more binding of labeled normal probesloss of
tumor DNA
Label probes for all tumor DNA
Metaphase chromosome
Hybridize to normal metaphase chromosomes for
4872 hours
Label probes for all normal DNA
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Genome-Wide Profiling Karyotyping
Different color probes for each chromosome
Hybridization for 2472 hours
Sorted, labeled human chromosomes
Human chromosomes
Microscope camera captures different spectra
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Genome-Wide Profiling Polymorphism Analysis
Person 2
Person 1
Common Sequence
Variations
Polymorphism
Variations in DNA
Deletions
Insertions
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Genome-Wide Profiling Gene Expression Profiles
What does my patients profile say about the
diagnosis? prognosis? treatment?
All LN breast tissue samples (metastatic)
LN
All LN- breast tissue samples (non-metastatic)
LN-
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Why Is It Important To Collect Genome-Wide
Profiles?
General population
Is there more cancer in group with suspected
SNP?
SNP suspected of link to cancer risk
Sort out people with telltale SNP
Lack suspected SNP
Analysis team
Have suspected SNP
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Can Genome-Wide Profiles Predict Cancer Risk?
Same profile, different environment different
result
No cancer
Cancer
Precancer
same genomic profile
cancer
same polymorphism
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Can Genome-Wide Profiling Discover Polymorphisms
That May Influence Cancer Risk?
Population
No Prostate Cancer
Prostate Cancer
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Can Genome-Wide Profiles Help Diagnose Cancer?
Diffuse large B-cell lymphoma under the microscope
Pathology sees one cancer
Patient 2
Patient 1
Diffuse large B-cell lymphoma after genome-wide
profiling
Region A
Molecular diagnosis sees two cancers
Region B
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Can Genome-Wide Profiles Inform Cancer Prognosis?
Patient DNA
21-gene panel linked to breast cancer recurrence
Parafin block
Patients tissue sample
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Can Genome-Wide Profiles Inform Cancer Treatment
Planning?
Colon cancer patients
Individual genome-wide profiles are sorted
Have mutated K-ras gene
Do not have mutated K-ras gene
Profile A... give targeted therapy A
A
E
A
B
C
C
B
B
C
A
E
E
A
E
B
C
B
C
B
C
B
Respond to targeted therapy A
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Can Genome-Wide Profiles Monitor the Response to
Cancer Treatment?
The goal verify that pathway is destroyed
mTOR?
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Will Genome-Wide Profiling Bring Personalized
Medicine for Cancer?
What does this profile mean in terms of my cancer
care?
Personalized Medicine for Cancer