Neoplasm III Flashcards
What does Retinitis (Xeroderma) Pigmentosum make people more susceptible to?
Increased risk of skin cancer in people exposed to UV light
Which gene is inherited in familial breast cancer?
BRCA1/BRCA2
What is a proto-oncogene?
A normal gene that can become an oncogene due to mutations or increased expression
How many alleles need to have an oncogene to cause a neoplasm?
Only one allele of a proto-oncogene needs to be mutated to cause neoplasia
How can proto-oncogenes be modified to create oncogenes?
Mutation, amplification, translocation
What is a tumour suppressor gene?
A gene that encodes proteins that suppress growth and therefore cancer
How many tumour suppressor genes need to be modified to create a neoplasm?
Both alleles of a Tumour Suppressor gene need to be mutated to produce neoplasia (Knudson’s 2-hit hypothesis).
What is Knudson’s 2 hit hypothesis?
Developed looking at retinoblastoma
2 hits needed for them to develop
Familial cancers - one hit immediately so higher risk of cancer
How is Ras important in the development of cancers?
Normally transmits growth-promoting signals to the nucleus
Mutant Ras is permanently activated resulting in continuous stimulation of cells
How is C-myc important in the development of cancers?
Binds to DNA, stimulates synthesis
Amplified (over-expressed) -Neuroblastoma, breast cancer
Translocation 8 –> 14 -Burkitt’s lymphoma
How is HER2 important in the development of cancers?
Encodes for a growth factor receptor
Amplified (over-expressed)
~25% of breast cancers
Herceptin is a competitive antagonist of HER2 receptor
Why is the pRB tumour suppressor gene important?
Passage beyond the R checkpoint at G1–>S boundary is governed by the phosphorylation of pRb.
A defect in both alleles of pRb leads to the cell escaping cell cycle control.
Retinoblastoma
Why is the p53 tumour suppressor gene important?
Approximately 50% of tumour contain p53 mutations
Gene encodes a nuclear protein, which binds to and modulates expression of genes important for cell-cycle arrest, DNA repair and Apoptosis
What is an initiator?
Carcinogenic agent
What is a promoter?
Enhance proliferations, especially in mutated cells and increase incidence of further mutations – can result in cancer
What does a cell need to become cancerous?
Initiators and promotors
How can radiation lead to cancers?
single/double strand breaks
base damage.
effect depend on the quality of radiation and the dose.
Name 2 radiations that can lead to cancer
UV
Ionising
How can chemicals lead to cancers?
Carcinogens interact with DNA in one of a number of ways.
Some act directly, others require metabolic conversion to an active form.
How are Polycyclic aromatic hydrocarbons produced?
Combustion of tobacco and fossil fuels
Hydroxylated into active form
How can Aromatic Amines lead to cancer?
Hydroxylated in liver and conjugated with glucuronic acid (Phase 2 drug metabolism, non toxic)
Deconjugated to active form in urinary tract by urinary glucuronidase
Active form sits in bladder –> Bladder cancer
Common in old dye workers
How can Alkylating Agents lead to cancer?
Bind directly to the DNA
An example is mustard gas
How can Hepatitis B lead to cancer?
Virus causes liver cell injury –> Regenerative hyperplasia
Increased cell division gives increased risk of genetic changes
How can Epstein Barr lead to cancer?
Infects epithelial cells or oropharynx and B cells
Viral genes dysregulate normal proliferative and survival signals
Sets the stage for acquisition of mutations
