Molecular biology

From Oncology for Medical Students
Ideal oncology curriculum > Molecular biology

Objective 2.4

At graduation, the student should be able to:

a) demonstrate an understanding of the molecular genetics of cancer: role of protooncogenes; tumour suppressor genes; DNA and RNA viruses; controls of apoptosis and angiogenesis; and elements of molecular genetic techniques
b) demonstrate an understanding of the molecular correlates of the pathological progression of cancer in a model system
c) describe hormonal influences and tumour markers relevant to tumour type and prognosis
d) identify important familial cancer syndromes and demonstrate an understanding of their molecular basis, mode of inheritance, associated risk of disease and implications for family counselling.

Prerequisite knowledge

  • Biochemistry
  • Functional anatomy
  • Genetics
  • Oncological physiology
  • Pathology

Representative questions that suggest the required depth of knowledge

1. Discuss oncogenes and their normal counterparts.

Essential in answer:

  • Normal functions of proto-oncogenes in the mitogenic cascade
  • Oncogenes as mutations of proto-oncogenes resulting in gain of function (dominant) characteristics
  • Examples of classes of normal functions (growth factors, their receptors etc)
  • Examples of mutating events (point mutation, amplification, translocation etc)

2. Approximately 70% of patients with retinoblastoma have unilateral disease and 30% have bilateral or multifocal disease. Explain the mechanisms for unilateral and bilateral disease. What is the risk of recurrence in family members?

Essential in answer:

  • Concept of RB1 as a tumour suppressor gene
  • Familial and sporadic cancers and the Knudson (two hit) hypothesis -- in familial retinoblastoma the first hit is either inherited or a new mutation in a gamete
  • Penetrance issues in familial cancers (bilateral disease always involves a germ-line mutation; unilateral disease may be familial so parents of an apparently sporadic case must be examined for evidence of healed retinoblastoma)
  • Familial cancers typically exhibit dominant inheritance with variable penetrance

3. A young woman consults you because she is anxious about her family history of breast cancer. Her mother died recently aged 53 of ovarian cancer following a history of breast cancer. She had two second-degree relatives with breast cancer, an aunt who died in her 40s and another aunt who died in her early 60s. Tissue is not available from any of the deceased relatives. What is this woman’s risk of cancer? What is your management rationale and why?

Essential in answer: If the diagnoses are correct and the deceased relatives are genetically related her risk of breast and ovarian +/- colorectal cancer is high (involvement of BRCA1 or 2 possible). Referral to a clinical geneticist or familial cancer clinic is desirable. The rationale for referral is to obtain risk assessment and management strategies which would include:

  • Counselling about risk and attitudes to genetic testing and information about its limitations (currently not available in Australia without DNA from an affected family member; false negatives)
  • Increased surveillance in the absence of testing or if gene mutation is detected
  • Identification of other family members at risk

4. Relate the following investigation findings to the appropriate tumour type:

(1) ovarian cancer
(2) breast cancer
(3) colorectal cancer
(4) prostate cancer
(5) hepatocellular cancer

(a) CA 15.3
(b) CA 19.9
(c) CA 125
(d) Prostate specific antigen (PSA)
(e) Carcinoembryonic antigen (CEA)
(f) Alpha fetoprotein (AFP)

Answer: 1c, 2a, 3e, 4d, 5f