CSIM 1.10 Neoplasia 5 Flashcards
Which populations are more likely to have cancers of a viral origin?
- Immunosuppressed patients
* Young patients (who may have less immunities)
What are the two groups that tumour-causing viruses fall into?
DNA oncogenic viruses
RNA oncogenic viruses
Which gene groups are found in call DNA oncogenic viruses? Which of these have roles in cellular transformation?
Early genes
• Control early events including replication of viral genome
• Has a role in cellular transformation
Late genes
• Control late events - synthesis of viral proteins, viral assembly and production
How do early genes affect cell transformation?
They encode transforming proteins which bind with growth-regulating proteins, such as retinoblastoma protein or p53
What are the three main DNA viruses in human tumours?
Herpes viruses
• Epstein Barr virus, Burkitt’s lymphoma and nasopharyngeal cancer
Papova viruses (e.g. HPV)
• HPV, cervical cancer
HepaDNA viruses
• Hepatitis B, heptocellular carcinoma
What are RNA viruses also known as?
Retroviruses
What is the only example of a cancer caused by an RNA virus?
Human T-cell leukaemia virus 1 (HTLV-1) from slow transforming retrovirus
What’s more important in cancer: genetic or environmental factors?
Environmental factors are significantly more important
What are the mechanisms of GENETIC (inherited) susceptibility?
Increased chance of a carcinogen reaching a target cell
• Pigmentation
• Varying metabolism of carcinogens
Inherit first step required for carcinogenesis (one of the two alleles
• Rb1 retinoblastoma
• p53 Li Fraumeni
Inherited instability of genome
• Inherited DNA repair gene defects
increased sensitivity to oncogenic viruses
• Immune status
• Different immune response to cancers
What is the inheritance pattern of cancer syndromes?
What are the key characteristics?
Autosomal dominant with incomplete penetrance
- Increased risk of tumours of specific sites and tissues (not general)
- Developmental abnormalities due to associated genes usually controlling cell cycle/apoptosis, etc
What is neurofibromatosis?
Which mutations can cause this?
Benign tumours of nerve sheaths
Caused by inherited mutations which inactivate one of two tumour suppressor genes:
• NF1, chromosome 17 normally inhibits RAS proto-oncogene
• NF2, chromosome 22 normally delivers signals which mediate contact inhibition
Which gene is a ‘gatekeeper’ gene which must often be mutated before the process of transformation can truly begin?
Which syndrome involves an inherited mutation of this gene?
How does this present?
APC (tumour suppression gene) which is usually one of the first mutations which has to occur in the stepwise process of carcinogenesis
Familial adenomatous polyposis
Thousands of polyps in colon, one of which will almost certainly become a colorectal carcinoma (so prophylactic stoma is needed)
How do familial cancers often present?
Cancers at a young age
No specific marker phenotype
What is an acquired pre-neoplastic lesion?
How does this happen?
An identifiable local abnormality associated with an increased risk of a malignant tumour developing at that site
There is increased proliferation of cells in regeneration, which is ‘fertile soil’ for the development of pre-neoplastic lesions due to the increased chance of acquiring genetic mutations
Why do periods of cell replication increase risk of tumours
Cell replication involves processes which may cause mutations (e.g. DNA replication), and also those cells with genes which are already damaged get replicated, providing a larger ‘pool’ of cells which are already one step towards a malignancy
