Lecture 22: Cancer File Flashcards
Cancer increases with…
age
Susceptibility to some cancers is familial (genetic), true or false ?
True
Explain germ line cells in terms of cancer
1 cell, mutations passed onto next generation
Differentiate into soma
Explain somatic cells in terms of cancer
Genetic dead end (mutations not passed on)
Disposable to natural selection
Are needed for germline cells
What cells are able to reproduce the organism
Germline cells = CAN reproduce the organism
SOmatic cells = CANNOT reproduce the organism
What cells have the higher mutation rate ?
Somatic cells have higher mutation rate than germ-line cells
A series of how many mutations is required for cancer to start ?
series of 5-6 mutations required
What are proto-oncogenes ?
Genes that encode proteins that stimulate cell proliferation
only need one copy to be mutated
Gain-of-function (dominant)
What are tumor suppressor genes ?
Genes that encode proteins that prevent cell proliferation
Need both copies to be mutated
Loss-of-function (recessive)
Proto-oncogenes are mutated to activated forms called……?
Oncogenes
Give an example of some oncogenes
RAS, Jun, Fos
Give an example of some tumor suppressor genes
Rb (Retinoblastoma), BRCA1 and BRCA2
What is the key step for developing a tumor of the retina (retinoblastoma) ?
Loss of a single gene (Rb)
What does the G1/S checkpoint do ?
Makes the decision whether to proliferate or not
What does Rb do to the G1/S checkpoint ?
It causes a break in it
Explain retinoblastoma in sporadic form
Affects older adults
tumour in one eye
Explain retinoblastoma in familial form
Affects children, ususally multiple tumors in both eyes
How is retinoblastoma treated ?
Tumor can be killed or eyes removed (90% survival rate)
Explain Kudson’s two hit hypothesis
In regards to a normal homozygous WT cell :
- at some point, a mutation arises. This is passed onto all daughter cells in heterozygous state, causing WT phenotype
- at another point, a secodn mutation occurs in the homologous gene in a daughter cel. This cell is homozygous mutant. This mutant cell has the mutant phenotype and proliferates more (one step towards cancer)
Use Kudsons two hit hypothesis to explain sporadic cancer
Two random somatic mutations are required in each copy of a gene in a single cell (thats why they are so rare)
Use Kudsons two hit hypothesis to explain hereditary cancer
One mutant germ line is inherited, so only one somatic mutation is needed to trigger cancer. Thats why it happens more in younger people and more often than once
What is the breast cancer associated gene ?
BRCA1
Is a loss-of-function allele (tumor supressor)
Increases risk to 90%
Give information on sporadic breast cancer
occurs in older women, one tumour, one breast
Give information on familial breast cancer
Younger women, multiple tumors, often affects both breasts
Are loss-of-functiion mutations or gain-of-function mutations easier to generate
loss-of-function mutations are easier to generate, but need two independant events in same cell
Gain-of-function mutations are rare, but only need one event