Genetic Testing in Genomic Medicine

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Genetic Testing in Genomic Medicine

• Gail H. Vance M.D.
• Professor, Department of Medical Molecular
  Genetics
• Indiana University School of Medicine

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Genomic Medicine

• The Human Genome Project completed in 2003
  provided access to the entire human gene sequence
  or genome..
• In effect, the genome is a set of tools enabling
  physicians to understand the biological and
  disease variability of their patients.

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Personalized Healthcare

• Understanding variability between individuals
  allows for more targeted or personalized
  healthcare based on genetic differences.

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Genetic Tests

• Genetic tests are powerful as they
• Diagnose the disease more precisely.
• Allow for selection of a specific medication to
  best treat the disease.
• Predict the risk of disease before symptoms
  occur.
• Manage the disease more effectively.

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Medicine of the past could be called
trial-and-error medicine
Observe
Diagnose
Treat
Monitor response
Adjust
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Because we know more specific information, we can
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Diagnose more precisely
Genetic tests identify DNA mutations of childhood
leukemia, enabling physicians to choose the
treatment that fits it precisely.
The impact of genetic tests and genome-based
cancer drugs on survival of childhood leukemia

• Acute lymphoblastic leukemia is most common form
  of childhood leukemia
• Genetic tests identify subtypes allow precise
  treatment and timing
• Todays cure-rate exceeds 80 vs. 4 in the 1960s

Source New England Journal of Medicine, 2006,
200l Personalized Medicine Coalition, 2006.
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Comparative Genomic Hybridization
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Select specific treatment

• A translocation between chromosomes 9 and 22
  results in a fusion gene formed from the BCR and
  ABL1 genes. The fusion on chromosome 22 is known
  as the Philadelphia chromosome and is
  characteristic of chronic myeloid leukemia.

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Chronic Myeloid Leukemia

• The BCR/ABL1 fusion results in increased cellular
  signaling causing white blood cell proliferation.
  
• Imatinib (Gleevec) is an oral medication that
  targets the translocation and arrests the
  disorder.

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Today, Cancer is experiencing a shift toward
precision medicine
Farber develops 1st chemotherapy for leukemia
Novartis launches Gleevec, the 1st molecular
targeted drug, to treat myeloid leukemia
2 types leukemia lymphoma
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2010
Disease of the blood
38 types of leukemia 51 types of lymphoma
3 types of leukemia (acute, chronic, preleukemia)
and 2 types of lymphoma (indolent, aggressive)
Source Mara Aspinall, Genzyme
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Genetic tests identify variations in the BRCA 1
and BRCA 2 genes that increase risks for breast
and ovarian cancer.
Predict Risk of Disease Before Symptoms

• Genetic tests identify greatly increased
  hereditary risk for breast and ovarian cancer
• Knowledge of increased risk allows preventive
  measures, such as closer monitoring, risk
  avoidance, and preventive surgery or chemotherapy

Lifetime risk of developing breast cancer
with BRCA 1 and 2 50 - 85
.without 13
Lifetime risk of developing ovarian cancer
with BRCA 1 and 2 10 - 45
without 1.7
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Hereditary predisposition for cancer

• Autosomal dominant inheritance
• high but incomplete penetrance
• variable expression
• Early-onset diagnosis
• Multiple cases of a cancer
• More than one primary cancer/Bilateral disease

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Molecular diagnostics is at the core of the
personalized medicine vision
Diseases will be diagnosed long before the
patient begins to manifest any evidence using
traditional tools
Molecular Diagnostics
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Managing Disease More Effectively

• Warfarin is an anticoagulant used to decrease the
  incidence of thromboembolisms (blood clots).
• Highly variable responses to the drug.
• Tight range of therapeutic response.
• Variants of two genes, CYP2C9 and VKORC1 account
  for 30-50 of the variability.

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Genomic medicine implies personalization and all
its benefits

• Diagnosis/ predicting risk of disease
• Determining whether a treatment is working
• Monitoring healthy people to detect early signs
  of disease
• Producing safer drugs by predicting potential for
  adverse effects earlier

• Producing better medical products
• Ready access to information
• Decreasing health care costs

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Genetic testing enables new way of thinking about
health reform
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The Promise of Personalized Healthcare

• Tailoring the diagnosis, prognosis, and treatment
  to the individual will improve healthcare
  outcomes and patient safety.

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A Primer on Genetic Testing What Is It? How
Does It Work? Why Does It Matter?
www.LabResultsForLife.com