Chapter 20: Genetics of Cancer Flashcards
Cancer is a genetic disorder at what level?
cellular
- Mutations alter ?
- _% mutations are germ line mutations (hereditary)
- gene expression
- 1%
What are four mutation sources for cancer?
- spontaneous
- radiation
- tumour viruses
- hereditary sources
What are the two types of tumours?
- Benign
- Malignant
Neoplasm?
- relentless growing mass which can be benign or malignant
Characteristics of a benign tumour?(6)
- edges are encapsulated
- no metastasis
- no invasion
- low growth rate
- normal nuclei
- not usually life threatening
Characteristics of a malignant tumour? (6)
- edges are irregular
- metastasis occurs
- invasion occurs
- high growth rate
- variable/irregular nuclei
- usually life threatening
Proliferation of cells is determined by what?
- cell cycle and its check points
What are the cell cycles check points?
- G1 to S
- G2 to M
- M checkpoint
Cell cycle checkpoints huh??
- they occur at different points in the cycle and are control points with which the cell cycle is arrested if there is damage to the genome or cell cycle machinery. This allows damage to be repaired or if it is not the cell is destroyed.
G1?
prepares the cell for DNA replication and chromosome duplication in the S phase….
G1 to S checkpoint?
-determines whether the cell is able to or should continue into S phase…..the cell stays in G1 unless it grows large enough and the environment is favourable.
G2-M checkpoint??
unless all the DNA has replicated, the cell is big enough and the environment is favourable the cell cannot enter the mitotic phase of the cell cycle.
M checkpoint?
- the chromosomes must attach properly to the mitotic spindle to trigger the separation of chromatids and the completion of mitosis.
Terminal differentiation?
cells that have lost the ability to proliferate; they have a finite lifespan; they are replaced by stem cells.
Cycle checkpoints are caused by what two things>
- cyclins (proteins)
- enzymes ( cyclin-dependent kinases)
Regulation of the Cell Cycle:
- Growth factors??
- growth factors are released: enhances proliferation—-> proto-oncogene
- growth factors are molecules that stimulate cell division of a target cell and have specific effects because they bind to specific receptors on the target cells.
Give a run through of the interaction of growth factors with a cell. (cell cycle regulation)
- GF binds to receptor (outside of cell/doesn’t enter the cell), activates receptor, signal is relayed through proteins in the cell, activates nuclear genes that encode for proteins that stimulate growth and division by affecting transcription factors.TF code for proteins that are released to stimulate cell division.
What about Growth inhibitory factors?
- they do the same run through as growth factors.
L> EXCEPT…..they activate nuclear genes that encode for proteins that INHIBIT growth and division.
L> Transcription factors in this case code for proteins that inhibit cell division
What are the three classes of genes that are relevant with cancer?
- proto-oncogenes
- Tumour suppressor genes
- Mutator genes
Proto-oncogenes??
L> normally?
L> cancer?
- Normal:
L>normally they stimulate cell division
L>proto-oncogene products are involved with stimulation of growth…ie growth factors, protein kinases, membrane associated g proteins
-Cancer:
L> mutant proto-oncogene (oncogene) are found in cancer cells, they are more active than normal or at inappropriate times.
Tumour suppressor genes???
L>normally?
L> cancer?
L>normally inhibit proliferation
L> in cancer cells they have lost their ability to inhibit proliferation ( division still occurs)
Mutator genes???
L> normally
L>cancer
L>normally ensure accurate replication and maintenance of the genome. (ensure DNA repair system is working accurately)
L> in cancer cells….they have lost this function and they make the cell prone to mutations in their genes…..( in either proto-oncogenes and tumour suppressor genes)
____ proto-oncogene mutation on a homologous pair of chromosomes is enough to cause an onocgene on that chromosome and to cause loss of cell division BUT you need more oncogenes to create a cancerous cell.
- 1
Cancer cells can result from ____ or untimely synthesis of _____ in cells that do not normally produce them. Change can also be caused by an alteration in ______(v-onc) or mutation of ___.
- excessive growth
- growth factors
- growth factor genes
- cellular proto-oncogene
Oncogenes are more ______ or active at ____.
- active than normal
- inappropriate times
Oncogenes can be caused by a tumour____.
- tumour virus
What are the two types of tumour viruses that can induce infected cells to proliferate and produce tumours?
- RNA tumour viruses
2. DNA tumour viruses
In terms of mutations what are the four kinds that can occur to bring about an oncogene?
L> how many are required for a proto-oncogene to be mutated into an oncogene ?
- deletion/point mutation
- gene amplification
- X rearrangement
- tumour virus
- a single mutation on a proto-oncogene can cause an oncogene on that chromosome
With RNA tumour viruses explain their oncogenes?
- they carry oncogenes that are altered forms of normal host genes.
Explain the infection process of an RNA tumour virus.
- infects cells, ssRNA genome is converted into a proviral dsDNA which than integrates into a chromosome of the host and creates RNA virus progeny.
- *** reverse transcriptase is what converts the ssRNA into ssDNA! then replication occurs making it ds
Retroviruses typically have three protein coating genes that are transcribed by host RNA _____ to get in new hosts and out of old ones to get into another. What are they?
- polymerase II
1. gag
2. pol
3. env
RNA Retrovirus genes:
1. Gag?
- encodes the precursor protein that cleaves to produce virus protein particles
RNA Retrovirus genes:
2. pol?
- encodes precursor protein that cleaves to produce reverse transcriptase ( to convert ssRNA to dsDNA - proviral) and integrase ( to integrate proviral DNA into chromosome of the host)