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?