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Summary of all molecular diagnostics lectures in Course 10
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Summary of all molecular diagnostic lectures (5) given in Course 10 (specialization biomedical research). Including notes of lectures and pictures.
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MOLECULAR DIAGNOSTICSMolecular diagnostics
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Lecture 1 03-02-‘21 ........................................................................................................................ 1
Translational medicine / research ....................................................................................................... 1
What is translational research? ....................................................................................................... 1
Diagnosis.......................................................................................................................................... 2
Characteristics of a good test: ......................................................................................................... 2
Understanding the role of imaging in cancer ...................................................................................... 2
Imaging ............................................................................................................................................ 2
Imaging: location ............................................................................................................................. 3
Imaging: drug discovery and functioning ........................................................................................ 5
Intra vital microscopy in drug behaviour ........................................................................................ 6
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, MOLECULAR DIAGNOSTICS
Lecture 1 03-02-‘21
MDX = advanced molecular techniques
Translational medicine / research
What is translational research?
The patient is in the middle of the screen (blue). We answer the questions that come from the
patients, we are the basic/bench.
Phases:
Phase I – medicine is save
Phase II – drug is effective
Phase III and phase IV
If the treatment works for the bigger population, but not for all the patients then the drug goes back
to the clinic and the phases start over to make the drug more effective for all patients.
1
, MOLECULAR DIAGNOSTICS
Diagnosis
• Emergency presentation
o Symptoms → poorer outcome
• Screening
o Imaging
▪ Mammography (breast cancer)
• Low-dose x-rays to detect cancer early – before women gets
symptoms – and it is most treatable
▪ Colonoscopy (colorectal cancer)
• CT
o Laboratory tests
▪ PAP test (cervical cancer)
▪ CA-125 (ovarian cancer)
▪ PSA (prostate cancer)
▪ BRCA1 (breast cancer)
Characteristics of a good test:
• Sensitive: detect small amounts, even in the presence of other molecules.
o Sensity gives information about the % of false negative samples.
• Specific: only the target molecule is detected (positive result).
o Specificity gives information about the % of false positive samples.
• Additional features of a good test:
o Potential for simple and standardized procedures
▪ Automation
o High throughput
o Cheap
o Complex biology
o Influence clinical decisions
o Majority is PCR-based
Understanding the role of imaging in cancer
Imaging
When/why is imaging used in (cancer) diagnostics?
• Location
• Stage of tumor (estimate)
• Growth
• Tumor dissection
• Plan treatment (localization of radiation)
• Monitor recurrence
• Intra vital imaging
• How drugs work and fail
2
, MOLECULAR DIAGNOSTICS
Imaging: location
• Based on e.g. (for example) interaction of electromagnetic radiation with body tissues and
fluids or sound waves.
We need to translate clinical questions to research. We need to dig deeper. We know that something
is off on the organ level, but not on the tissue or molecular level.
• Why do some tumors grow faster?
• Why are some patients resistant to therapy?
• Why do some tumors recur more often?
• Why and how do some tumors metastasize (spread from one part of the body to the other)?
o Proliferation
o Angiogenesis = development of new blood vessels
o Migration
o Apoptosis
Why do some tumors grow faster?
Example: breast cancer
• Human epidermal growth factor receptor (HER2) on tissue
and cellular level.
• HER2 amplification (uitbreiding) in 20-30% breast carcinomas
• Patients have more HER2 in their cells. 20-30% of the
patients have an increased HER2 number.
• > HER2 → shorter survival, bad therapeutic response
• First, we should know whether the patient has increased
HER2 on the cells. If that is the case, then we can measure
presence of HER2 using FISH.
o FISH = fluorescent in situ hybridization
o Labelled copy of the target sequence. The probes are
fluorescent labelled probes.
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