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Understanding Genome-Wide Profiling of Cancer Donna Kerrigan, M.S. E. Milliken, Ph.D. L.M. Bennett, Ph.D. Erin Milliken L. Michelle Bennett.

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Presentation on theme: "Understanding Genome-Wide Profiling of Cancer Donna Kerrigan, M.S. E. Milliken, Ph.D. L.M. Bennett, Ph.D. Erin Milliken L. Michelle Bennett."— Presentation transcript:

1 Understanding Genome-Wide Profiling of Cancer Donna Kerrigan, M.S. E. Milliken, Ph.D. L.M. Bennett, Ph.D. Erin Milliken L. Michelle Bennett

2 Single Gene Tests: A Locally Focused Search Chromosome ContinentCountryU.S. StateWorld Genome Cell Chemical bases Gene AG TC

3 Genome-Wide Profiling: A Globally Focused Search Chromosome ContinentCountryU.S. StateWorld Genome Cell Chemical bases Gene AG TC

4 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

5 Genome-Wide Profiling: Many Ways

6 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

7 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

8 Genome-Wide Profiling: Polymorphism Analysis Variations Person 2Person 1 = Variations in DNA Common Sequence Insertions Deletions Polymorphism

9 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

10 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

11 Can Genome-Wide Profiles Predict Cancer Risk? = same genomic profile Same profile, different environment = different result No cancerCancerPrecancer = cancer= same polymorphism

12 Can Genome-Wide Profiling Discover Polymorphisms That May Influence Cancer Risk? No Prostate Cancer Population Prostate Cancer

13 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

14 Can Genome-Wide Profiles Inform Cancer Prognosis? Patient’s tissue sample Patient DNA 21-gene panel linked to breast cancer recurrence Parafin block

15 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 AEA A A EE E BCC BC B BC BC BCB

16 Can Genome-Wide Profiles Monitor the Response to Cancer Treatment? The goal: verify that pathway is destroyed mTOR↓

17 Will Genomically Informed Cancer Care Be Better for Patients? Customized Care What does this profile mean in terms of my cancer care?


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