DNA Based Diagnostics and Treatment

DNA Based Diagnostics and
Names: Anam Quraishi, Andrew Girgis, Qurat-Ul-Ain Jalal
September 23rd, 2013
PHM142 Fall 2014
Instructor: Dr. Jeffrey Henderson
Case Study
• A recently diagnosed breast cancer patient is in the
inpatient oncology department, with a hospital
pharmacist who specializes in breast cancer.
• She wants to know if she is eligible to participate in
a novel clinical trial.
• She is in need of relevant information on how the
clinical trial will work and how it will benefit her.
• How can we help!?!
Next Generation Sequencing!
• The bases in a small fragment of DNA are
sequentially identified from signals emitted
as each fragment is re-synthesized from a
DNA template strand
• Produces millions of sequences in a parallel
• Unlike other proceses which are limited to
just a few DNA fragments
• Produces hundreds of gigabases of data in a
single sequencing run
• Low cost, high throughput alternative
Next Generation Sequencing!
• Powerful tool for whole genome sequencing in lab environment
• Using prior technology, sequencing an entire genome required a lot of time &
• NGS allows for a whole genome to be sequenced in a few days
• Scalability allows for it to be useful for viral/bacterial genomes along with large
human genomes
• Allows for better understanding of genetic mutations
Detection of Mutations in Cancer
• Need reliable detection of mutations within an
individual cancer genome
• Current techniques include: immunohistochemistry,
histological analysis, PCR and traditional sequencing
• NGS allows for detailed information on individual
• Decrease in cost and increase in accuracy of
sequencing with NGS
• Future of cancer genomics is underpinned by NGS
• The Cancer Genome Atlas: catalogue of genetic
mutations responsbile for cancer
Detection of Mutations in Cancer
• DNA-based diagnostic tests could
determine the sites of methylation on
tumor suppresor genes which leads to
their silencing, and contributes to the
development of cancerous tumors.
• Development of drugs that prevent
this methylation might be used for
therapeutic means.
• The progression of the disease state
can also be monitored by this efficient
DNA-based diagnostic test.
Detection of Other Diseases
Cardiovascular Diseases
Metabolic Disorders
Infectious Diseases (AIDS,
tuberculosis, Hepatitis C, Lyme
• Sexually transmitted diseases
(Pappiloma virus, chlamydia, herpes)
• Presense of bacteria or virus in a
• Prenatal diagnosis of genetic disorders
• More!
Other DNA-based diagnostic methods
• PCR (real-time PCR, quantitative PCR, reverse transcriptase PCR, etc.)
• Traditional sequencing
• Microarrays (Single Nucelotide Polymorphism oligomicroarrays, array
comparative hybridization, fluorescence in-situ hybridization)
• Southern Blotting
How is this relevant for Pharmacists?
• Pharma companies are interested in
knowing how their drug will affect the
disease at the molecular level.
• Pharmacists need to be able to
counsel patients on personalized
medications, based on the diagnosis
made by these dna-based diagnostic
• DNA-based diagnostics tests are a fast
and efficient way to detect, and also
monitor the progression of disease or
impact of drugs.
Closing the case
• Identify's patients eligibility for the clinical
trail and refer patient to enrol in the clinical
trial, if applicable.
• NGS identified patient's tumor harbours
PIK3CA mutation (prevalent in about 36% of
breast cancers)
• Also utilizing NGS, a luminal A expression
subtype was confirmed (ER+/ERRB2+ and
PR+ and HER2 negative)
• Favourable prognosis out of breast cancer
subtypes (slow growing and non-invasive)
Summary Slide
• Next Generation Sequencing: The bases in a small fragment of DNA are
sequentially identified from signals emitted as each fragment is re-synthesized
from a DNA template strand
• Advantages: whole genome sequencing in a matter of days, low cost, high
accuracy. Sequences millions of DNA fragments concurrently
• Diagnostically useful for: Cancers, infectious diseases, metabolic disorders,
prenatal diagnosis, identifying presence of virus or bacteria, etc.
• Other diagnostic methods : PCR, microarrays, southern blotting
• Relevance to Pharmacists: personalized medicine, designing specific drugs and
studying their effects, monitoring disease states, counselling .
• D. M. Vasudevan, S. Sreekumari, Kannan Vaidyanathan, Textbook of Biochemistry for Medical Students (text
book link can be found here:
• Idris, S. F., Ahmad, S. S., Scott, M. A., Vassiliou, G. S., & Hadfield, J. (2013). The role of high-throughput
technologies in clinical cancer genomics. Expert review of molecular diagnostics, 13(2), 167-181.
• Simon, R., & Roychowdhury, S. (2013). Implementing personalized cancer genomics in clinical trials. Nature
Reviews Drug Discovery, 12(5), 358-369.
• http://res.illumina.com/documents/products/illumina_sequencing_introduction.pdf
Magdalena Cizkova et al. (2012) PIK3CA mutation impact on survival in breast cancer patients and in ERα, PR and ERBB2-based
subgroups. Breast Cancer Research and Treatment, 14:R28.

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