Paper I
Question
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- (a) Define neoplasia. ( 2 mark(s)
- (b) Enumerate the four classes of normal regulatory genes, with one example each, that are the principal targets of genetic damage leading to carcinogenesis. ( 4 mark(s)
- (c) Write a note on how viruses are implicated in carcinogenesis with examples. ( 4 mark(s)
- (d) Tabulate the salient differences between benign and malignant tumors. 5 mark(s)
Answer
(a) Definition of neoplasia
- Neoplasia is the abnormal, uncontrolled, and autonomous proliferation of cells that persists even after the initiating stimulus has been removed, resulting in a mass of tissue (neoplasm/tumour) whose growth is uncoordinated with that of normal tissues
(b) Four classes of normal regulatory genes targeted in carcinogenesis
- Proto-oncogenes (growth-promoting genes) — e.g., RAS
- Tumour suppressor genes (growth-inhibiting genes) — e.g., TP53
- Genes regulating apoptosis — e.g., BCL2
- DNA repair genes — e.g., BRCA1/BRCA2, mismatch repair genes (MLH1, MSH2)
(c) Viruses implicated in carcinogenesis
- HPV (Human papillomavirus): E6 protein degrades p53; E7 protein inactivates Rb — implicated in cervical carcinoma
- HBV/HCV (Hepatitis B/C virus): Chronic inflammation, liver cell injury/regeneration, and (for HBV) direct integration into host genome — implicated in hepatocellular carcinoma
- EBV (Epstein-Barr virus): Implicated in Burkitt lymphoma, nasopharyngeal carcinoma, some Hodgkin lymphomas
- HTLV-1 (Human T-cell lymphotropic virus-1): Tax protein activates cellular growth pathways — implicated in adult T-cell leukaemia/lymphoma
- HHV-8 (Kaposi sarcoma herpesvirus): Implicated in Kaposi sarcoma
(d) Differences between benign and malignant tumours
| Feature | Benign | Malignant |
|---|---|---|
| Growth rate | Slow | Rapid |
| Growth pattern | Expansile, well-circumscribed | Infiltrative, poorly circumscribed |
| Capsule | Often encapsulated | Usually unencapsulated |
| Differentiation | Well differentiated | Variable, often poorly differentiated |
| Mitotic activity | Low, normal mitoses | High, atypical mitoses |
| Local invasion | Absent | Present |
| Metastasis | Absent | Present |
| Recurrence after excision | Rare | Common |
| Systemic effects | Usually minimal | Cachexia, paraneoplastic syndromes common |