Cancer Genes & Genetics Flashcards
Hallmarks of Cancer
(6)
What is cancer?
Uncontrolled growth/proliferation of abnormal cells
A heterogeneous mixture of cells
What is the difference between hetero and homogeneous cancers?
Homogeneous tumours can be more easily eliminated by treatments, but in heterogeneous tumours, some resistant clones will survive cancer therapy selective pressures and repopulate the tumour. This means these cancers need combination therapies.
Steps in the formation of a tumour.
Tumourigenesis (Primary Tumour) Angiogenesis Detachment / Invasion Intravasation Migration / Transport Extravasation Micrometastasis Macrometastasis (Secondary Tumour)
4 treatments of cancer
- Surgical removal or radiation of primary tumour
- Chemotherapy to limit spread and proliferation of tumour cells
- Immunotherapy to stop immune evasion
- Correct the dysregulated signalling pathways
The evidence that cancer is a genetic disease (5)
- most carcinogens are also mutagens
- it is not contagious
- incidence increases with age (as does DNA damage, CI)
- some cancers segregate in families
- DNA repair gene defects increase cancer probability
Germline and somatic mutations
Germline - every cell in the body, including reproductive cells. Passed from parent to child and are less common.
Somatic - Acquired in a sporadic manner. Non-inheritable and occur from gene damage in a person’s lifetime.
What are oncogenes?
Example
Proto-oncogenes carry out normal functions in cell homeostasis.
Dominantly acting, gain a function when mutated.
Not inherited because active oncogenes affect germline development and cause lethality.
Promote cell growth/division
Only one copy needs to be mutated to have an effect.
Occurs through translocations, point mutations or gene amplification
EX - H-Ras - single base pair mutation causes overactivity in bladder carcinomas.
What are tumour suppressors?
Example
Recessively acting
Inherited in familial cancer syndromes
Mutations in tumour suppressors that usually function to prevent cell growth and proliferation, mutations turn these off.
Examples - APC in FAPC
What are gatekeepers, caretakers and landscapers?
Gatekeepers - classical tumour suppressor genes that act to directly restrain cell proliferation.
Caretakers - act indirectly to maintain the integrity of the genome.
Landscapers - act indirectly to control the environment in which cells grow. Creates a microenvironment to aid cancer growth.
What are DNA repair genes?
Indirectly involved with growth inhibition / differentiation.
Inactivation of these genes increases the amount of unrepaired DNA damage and accumulation of mutations in other parts of the genome.
Increased likelihood of damaging mutations occurring in other critical genes.
What is retinoblastoma and the two forms of it that can occur?
Retinoblastoma is the most common eye tumour seen in children.
Has inherited and sporadic forms.
Inherited = bilateral, diagnosed before 1yr and has an increased chance of secondary tumour.
Sporadic = unilateral, diagnosed at approx 2yrs, no secondary tumour chance.
What is the two-hit hypothesis?
How is this related to the inherited form of retinoblastoma?
2HH = When one mutation in an allele is passed down in the germline, only one sporadic mutation is needed for both the alleles to be mutated and the loss of tumour suppression.
Inherited retinoblastoma is autosomal dominant in transmission. Retinal cells grow very rapidly in early life, so the likelihood that a sporadic mutation occurs to cause the cancer when one is already mutated in the germline is much higher than two separate sporadic mutations.
What is loss of heterozygosity?
2 separate mutational events disrupting both alleles in a cell is unlikely to occur.
The second mutation in sporadic cancers is caused by a recombination event that leads to a loss of the wild type
What is haploinsufficiency?
Some tumour suppressor genes require both alleles to function correctly suppress oncogenesis. So one mutation is enough to deactivate.
EX - PTEN
