Tumour Pathology 5 Flashcards
Describe how B-Raf has a role in melanoma.
Malignant melanoma is a cancer usually caused by BRAF - commonest mutation to BRAF changes a valine for glutamic acid at amino acid number 600.
The mutated product = BRAF V600E = ONCOGENE
This switches BRAF on all the time - independently, and pushes the cell cycle forward.
Describe how HER-2 has a role in breast cancer.
HER-2 is a normal molecule in our body.
Mutation - that causes an overexpression of HER-2.
Overexpression of HER-2 means that the receptor can bind more growth factors and means that the cell cycle can be pushed forwards.
Describe how retinoblastoma gene product has a role in retinoblastoma (retinal cell cancer).
Normal, healthy people have 2 copies of retinoblastoma gene product (one from each parent).
In hereditary causes, mutation causes one gene to stop making protein, but it still leaves the other gene producing protein.
If there is NO retinoblastoma gene product, and the E2F molecules are released and can progress the cell cycle, then retinoblastoma malignancy can occur.
Describe healthy B-Raf.
B-Raf is an example of a transduction molecule (that is part of a chain of molecules).
BRAF gene is a proto-oncogene
Describe the causes of mutation of B-Raf in melanoma
Rarely ever hereditary when it comes to proto-oncogenes.
Environmental = UV radiation damages the DNA inside the nucleus of the cell.
Describe retinoblastoma gene product.
This protein is fundamental to the replication of cells.
A tumour suppressor gene, when it has only a few phosphates added, it blocks progression of the cell cycle.
Describe how mismatch repair genes - MLH1 have a role in cancer
MLH1 gene makes MLH1 protein.
MLH1 in conjunction with other proteins, can recognise and locate the DNA base pair mismatch - fixes the error and stops the cell division (by inducing p53).
Describe how MLH1 has a role in colon cancer.
Mutation in MLH1 can cause reduction in the amount of its protein = decreased mismatch repair.
If the mutation remains and is replicated and repaired over and over again.
- DNA polymerase (enzyme that replicates DNA) may slip, and cell starts to accumulate all sorts of mutations as it divides.
= Colon cancer
Adenocarcinoma.
Describe the role that p53 has in certain cancers.
p53 is a tumour suppressor gene that
Describe how mutated p53 occurs from smoking.
There are numerous chemicals in cigarette smoke - they are metabolised in the liver and released into the circulation - this damages DNA - numerous mutations (if MLH1 cannot fix these mutations)
- mutation in p53
Describe how mutated p53 can occur from radiation.
Sunlight UV radiation lands on top part of bottom lip of mouth - Mutations in several genes e.g. mutations in p53 - increased risk of cancer.
Describe how mutations in p53 can arise from Human Papilloma Virus.
Infection of cervix - produces E6 protein which binds and inactivates p53 (also produces a protein which binds and inactivates retinoblastoma gene product).
Increased risk of subsequent uncontrolled cell division, precancer and then cancer.
Describe the function of c-myc.
Increases many proteins which push the cell towards cell division.
Increases other proteins which stop cell death.
Overall effect is to promote increased number of cells - proto-oncogene.
More likely to proliferate.
Normally tightly controlled.
Describe the process of overexpression of c-myc.
Sometimes due to an event (e.g. radiation), part of chromosome 8 breaks off and translocates to chromosome 14. t(8:14)
c-myc sticks onto a regulatory sequence (for immunoglobulin), HUGE production of c-myc.
This pushes cell cycle forward and stops cells dying.
Promoting cancer
Over-expressed c-myc is acting as an oncogene.
Describe how alcohol could cause cancer.
Small amounts of alcohol are completely metabolised in liver.
Larger amounts - converted to acetyl aldehyde which then gets into systemic circulation, causing a double strand break in DNA in many genes - increased risk of cancer.
