Week 13 - Molecular Basis of Cancer Flashcards
Cancer commonly occurs due to the mutation of
- Protooncogenes - gain of function mutation into oncogene which increases rate of cells through the cell cycle - uncontrolled cell proliferation
- Tumour Suppressor Genes - loss of function mutation - results in moving cells faster through the cell cycle - uncontrolled cell proliferation
Why does cancer occur
Cancer occurs due to an accumulation of gene mutations within any nucleated cell in the body.
Explain how cancer has genetic variance in cancer daughter cells
Cancer is a progressive disease and its unstable genetic repair mechanisms lead to the division of cancer cells into not perfect copies of itself, resulting in new populations of mutants developing
Why is the genetic diversity in cancer tumours bad
This genetic variance allows cancer to respond to the forces of evolution. It also makes chemotherapy not as effective as the drug can only target certain cell mutations, leaving the others still active
What is the integrated circuit of the cell
the way that cells function using signal transduction pathways which communicate intracellular functions such as cell replication. However if these signal pathways are broken, due to mutations in the gene it will result in abnormal outcomes.
Why are older people more likely to develop cancer
It takes time for mutations to occur and accumulate, within any one specific cell. Hence as you age the amount of mutations acre within the body increase, increasing the like-hood of developing cancer.
Why it is more likely for cells that are already rapidly dividing to develop into cancer, than it would be for something like a neuron which don’t undergo cell division?
More a neuron to progress down the pathway of tumorigenesis and gain all of the functions of cell proliferation, dediffereation, invasiveness and metastasis, it will require to gain mutations which enable it to do those functions (as it doesn’t already undergo those functions). However in cells which already have the genes turned on for cell proliferation, it doesn’t need to mutate though as many functions, hence it is easier for cancer to occur in these cells.
How does somatic mutations impact the next generation
Cancer is commonly caused by mutations to somatic cells, and develop after birth from a variety of reasons. These mutations are not passed onto the next generation.
Cancer itself cannot be passed through generations, as a baby cannot be born with cancer.
How does germline mutation impact the next generations
The cancer itself cannot be passed on to off springs. However mutations in gametes (risk alleles) can be passed on, increasing the off springs susceptibility of developing cancer
Explain the example of retinoblastoma mutation
Retinoblastoma Gene 1 is a protein (tumour suppressor gene) which prevents cells from progressing through the cell cycle. However a loss of function mutation can lead to uncontrolled cell proliferation and retinoblastoma in the retinoblasts which is exposed to high levels of UV radiation.
Why is there a heterozygous disadvantage in retinoblastoma
If born heterozygous for a non functional retinoblastoma gene 1 - meaning one eye has the protein while the other does. This causes the change of developing retinoblastoma to be far higher because only the other healthy allele needs to be mutated before the uncontrolled cell proliferation to occur instead of 2 alleles.
Explain the example of mutations to the Ras gene
The Ras/Raf/MAPK pathway controls how cells receives signals from growth factors to begin cell proliferation.
A gain of function mutation to Ras would result in promotion of cell through the cell cycle without stimulation from other proteins. This results in uncontrolled cell proliferation
What are the 4 major types of DNA damage
- Single strand break/single base damage
- Bulky lesions/Crosslinks - instead of forming h-bonds with the complementary strand nucleotides form H-bonds with nucleotides next to them
- Base mismatch - the nucleotide base pairs are not complementary
- Double-strand break
What are examples of DNA repair systems
- Nucleotide Excision Repair - for cross links
- BRCA gene
Explain BRCA gene as a site of mutation
Breast Cancer susceptibility protein (BRCA) type 1 and type 2 are both DNA repair proteins.
Forms BASC complex to function
This gene is able to repair single base damage and double strand breaks.
However they go under a loss of function mutation the body will no longer be able to repair DNA effectively.
