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Understanding Genome-Wide Profiling of Cancer
Donna Kerrigan, M.S.
E. Milliken, Ph.D.
L.M. Bennett, Ph.D.
Single Gene Tests: A Locally Focused Search
Chromosome
Continent Country U.S. StateWorld
Genome
Cell
Chemical basesGene
A G
T C
Genome-Wide Profiling: A Globally Focused Search
Chromosome
Continent Country U.S. StateWorld
Genome
Cell
Chemical basesGene
A G
T C
Starts with Proper Collection and Storage
Informed consent
Carefully refreeze
Carefully retrieve and
analyze
StoreAdd unique identifier
Post-acquisitionPre-acquisition
Biopsy sample
The specimen is biologically viable
Genome-Wide Profiling: Many Ways
Genome-Wide Profiling: Comparative Genomic Hybridization
Label probes for all
tumor DNA
= equal binding of labeled normal and tumor probes
= more binding of labeled tumor probes—gain of tumor DNA
= more binding of labeled normal probes—loss of tumor DNA
Metaphase chromosome
Hybridize to normal metaphase chromosomes for
48—72 hours
Label probes for all
normal DNA
Genome-Wide Profiling: Karyotyping
Sorted, labeled human chromosomes Microscope camera
captures different spectra
Different color probes for
each chromosome
Hybridization for 24—72 hours
Human chromosomes
Genome-Wide Profiling: Polymorphism Analysis
Variations
Person 2Person 1
= Variations in DNA
Common Sequence
Insertions
Deletions
Polymorphism
Genome-Wide Profiling: Gene Expression Profiles
All LN+ breast tissue samples
(metastatic)
What does my patient’s profile
say about the diagnosis?prognosis?treatment?
Lymph node negative
All LN- breast tissue samples
(non-metastatic)
Lymph node positive
Why Is It Important To Collect Genome-Wide Profiles?
Lack suspected SNP
Is there more cancer in group with
suspected SNP?
Analysis teamHave suspected SNP
Sort out people with telltale SNP
SNP suspected of link to cancer risk
General population
Can Genome-Wide ProfilesPredict Cancer Risk?
= same genomic profile
Same profile, different environment = different result
No cancerCancerPrecancer
= cancer= same polymorphism
Can Genome-Wide Profiling Discover Polymorphisms
That May Influence Cancer Risk?
No Prostate Cancer
PopulationProstate Cancer
Can Genome-Wide Profiles Help Diagnose Cancer?
Diffuse large B-cell lymphoma after genome-wide profiling
Molecular diagnosis sees two cancers
Pathology sees one cancer
Diffuse large B-cell lymphoma under the microscope
Patient 2Patient 1
Region B
Region A
Can Genome-Wide Profiles Inform Cancer Prognosis?
Patient’s tissue sample
Patient DNA
21-gene panel linked to breast cancer
recurrenceParafin block
Can Genome-Wide Profiles Inform Cancer Treatment Planning?
Individual genome-wide profiles are sorted
Colon cancer patients
Have mutated K-ras gene
Profile A...give targeted
therapy A
Respond to targeted therapy A
Do not have mutated K-ras gene
A E A
A
AEE
E
B C C
B C
B
BC
B C
B C B
Can Genome-Wide Profiles Monitor the Response to Cancer Treatment?
The goal: verify that pathway is destroyed
mTOR↓
Will Genomically Informed Cancer Care Be Better for Patients?
CustomizedCare
What does this profile mean in terms of my
cancer care?