Molecular Pathology of Tumours Flashcards
What are the properties of malignant cells?
Disordered proliferation, apoptosis, differentiation, and relationship with the surrounding environment (invasion, metastasis, angiogenesis).
What does the multi-step process of carcinogenesis imply?
Cancer development involves multiple genetic alterations over time.
What does clonality suggest about tumour development?
Tumours arise from a single cell that has undergone genetic changes.
What are oncogenes?
Genes that drive neoplastic behaviour when activated.
What are proto-oncogenes?
Normal genes that have the potential to become oncogenic.
What are tumour suppressor genes?
Genes that inhibit cell proliferation or promote cell death, particularly in cells with DNA damage.
How do oncogenes function in tumours?
By stimulating cell cycle transcription, activating growth factor receptors, increasing growth factor production, and interfering with intracellular signaling.
Give examples of oncogenes and associated cancers.
sis (growth factor) – fibrosarcoma
HER2 (receptor) – breast cancer
ras (signal transducer) – colon cancer
myc (transcription factor) – Burkitt’s lymphoma
What is Knudson’s two-hit hypothesis?
Both alleles of a tumour suppressor gene (e.g., RB) must be inactivated for cancer to develop.
What is the role of RB in carcinogenesis?
RB is a gatekeeper that inhibits proliferation or promotes death of cells with DNA damage.
What is a caretaker gene?
A gene that maintains genome integrity by promoting DNA repair.
Examples of diseases linked to defective caretaker genes?
Xeroderma Pigmentosa (nucleotide excision repair)
Hereditary non-polyposis colon cancer (mismatch repair)
What is the role of p53 as a gatekeeper and caretaker?
p53 regulates cell cycle, promotes apoptosis, and responds to DNA damage.
What syndrome is associated with p53 mutation?
Li-Fraumeni syndrome
What enables tumour angiogenesis?
Tumour cells activate pathways that promote new blood vessel formation.
What molecular changes lead to invasion and metastasis?
Loss of cell adhesion
Binding to basement membrane via laminin receptors
Secretion of proteolytic enzymes (type IV collagenase, plasminogen activator)
Basement membrane degradation and cell migration
What are the ‘7 deadly sins’ of tumour cells?
- Self-sufficiency in growth signals
- Insensitivity to growth-inhibitory signals
- Evasion of apoptosis
- Defects in DNA repair
- Limitless replicative potential
- Sustained angiogenesis
- Ability to invade and metastasise
What is the role of telomerase in tumour cells?
Telomerase extends the lifespan of cells, contributing to limitless replication and immortalisation.
How does telomerase contribute to tumorigenesis in culture?
Its introduction immortalizes cells, mimicking the behaviour of cancer cells.
