Lecture 6: Molecular Diagnostics

Question 1

What are the general categories of disease?

Answer 1

Hereditary diseases, infection diseases, inflammatory disease, and neoplastic diseases

Question 2

How can genetic alterations cause disease?

Answer 2

Loss or reduction of normal levels of gene expression causes loss of protein function, or a protein that functions incorrectly.
Increased levels of gene expression, which result in overexpression of a protein.

Question 3

How can DNA biomarkers be acquired from a patient?

Answer 3

Using various non-invasive, or invasive procedures. Such as an oral swab, or an invasive spinal tap.
Tissue biopsy can be performed for molecular testing or routine pathologic examination.
Sometimes molecular biomarkers are left by presence of viruses or bacteria.

Question 4

What molecular alterations are present in breast cancer?

Answer 4

While typically just one type (invasive ductal carcinoma), each type of cancer has unique patterns of alterations in the genome, this creates a various number of biomarkers that can be tested for.

Question 5

What is targeted therapy?

Answer 5

Personalised medicine, once a diagnosis has been confirmed with clinical symptoms and pathological investigation. Once a genetic cause has been identified this can allow the use of specific therapies and drugs.
For example Tamoxifen is used in treatment of oestrogen receptor-positive (ER1) breast cancer, whereas Herceptin is used in human epidermal growth factor 2 positive (HER2) breast cancer.

Question 6

What aspects of a tissue sample are analysed in molecular pathology?

Answer 6

Morphological, immunohistochemical and molecular features.

Question 7

What should a molecular pathology report contain?

Question 8

What can molecular tests of tissue samples be used to predict?

Answer 8

Can affect a prognosis, predicting factors such as:
- Relapse-free survival
- Probability of recurrence
- Probability of progression to metastatic disease (in example of cancer)
- Overall survival.

Question 9

What determines if a mutation is relevant or not?

Question 10

What complicating factors are there when treating tumours?

Question 11

What different tests are used for the various causes of tumours?

Answer 11

• Mutation in individual genes/infection organisms (PCR)
• Abnormalities of overall chromosome structure, predominantly fluorescence in situ hybridisation (FISH)
• Abnormalities in RNA, chromogenic in situ hybridisation (CISH)
  Changes in protein expression, immunohistochemistry (IHC) and OSNA.