MCB Lecture 23 Cancer Flashcards Preview

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Flashcards in MCB Lecture 23 Cancer Deck (53)

What are the cancer trends in Australia currently?

For the past 20 years, incidence has increased, but the rate has stayed roughly constant


What are the Big 5 cancers?

Skin melanoma


How many deaths per year do the Big 5 represent collectively?



Has there been any improvement in the cancer incidence rate in Australia?

Yes in some cancers there has been some improvement in morbidity

However, in pancreatic and lung, there has been little to no improvement


What does the term cancer refer to?

Cancer is a generic term for a collection of generic terms


What are the four general types of cancer?

1. Carcinoma: cancer of epithelial cells
2. Sarcoma : cancer of connective tissue
3. Lymphoma: cancer of lymphatic system
4. Leukaemia: cancer of blood cells


What are sarcomas?

Cancers of connective tissue


What are carcinomas?

Cancer of epithelial cells


What are leukaemias?

Cancers of blood cells


What are lymphomas?

Cancer of the lymphatic system


What is the relationship between cancer incidence and age?

As age increases, cancer incidence increases


Describe delayed onset

Cancer onset will be a number of years after the exposure to the carcinogen


What are the two types of tumours?

Benign and malignant


What is a benign tumour?
Give an example

Benign tumours do not invade healthy tissues and cause spread of cancerous cells

Cannot create new tumours

Eg. Freckles and moles


What is a malignant tumour?

These tumours can invade healthy tissues, metastasise and cause more tumours


What is metastasis?

This is when cancerous cells are mobile. They move from one area to another.
This may be from the origin to elsewhere, or not


What is the name for the process where a normal cell becomes cancerous?
How does this occur?

Malignant transformation

This occurs when there is a build up of mutations, eventually leading to a cell that has uncontrolled cell division etc.


What is apoptosis?

Programmed cell death


What is senescence?

When a cell is still alive, but is not still growing


What are the two main pathways to tumourigenesis?

1. Activation of tumour promoting
2. Deactivation of tumour suppressing


Give a general description of the tumour promoting pathway

Mutation relating to a proto-oncogene

Proto oncogene becomes an oncogene --> increase is cell proliferation


What is an oncogene?

An oncogene is a gene relating to functions such as cell proliferation that has been over expressed somehow, turning a normal cell into a cancerous cell


What is a proto-oncogene?

This is the normal version of the cancer causing gene.
It has a role in cell proliferation


What are the 5 different ways that proto-oncogenes can be turned on?

1. Mutation causing hyperactive protein made in normal amounts
2 mutation in promoter region causing normal protein to be made in increased amounts
3. Gene replication: multiple copies of the gene
4. Chromosome rearrangement:
a. Gene comes near regulatory sequence
b. fusion to an actively transcribed gene causing a hyperactive protein


What does a deletion/SNP in a proto-oncogene lead to?

The gene product may have increased activity
Now, the same amount of the protein has a bigger effect on the cellular processes


What does a mutation in the regulatory sequence lead to?

Overproduction of a normal gene


What does gene amplification of proto-oncogenes lead to?

Overproduction of a normal protein


What does chromosome rearrangement involve?
What are the two examples of chromosome rearrangement?

a. Sequence fused near regulatory sequence --> Burkit's lymphoma
b. Sequence fused to an actively transcribed gene -> Chronic Myeloid Leukaemia


How is Burkitt's lymphoma caused?

Fusion of regions from Cr. 8 to Cr. 14
Myc fused to immunoglobulin regulatory region


How is Chronic Myeloid Lymphoma caused?

Regions from Cr. 9 and Cr. 22 become spliced
Abl gets spliced to bcr

The Philadelphia chromosome


Which two regions are fused in the Philadelphia chromosome?
What does each region do?

bcr: break point cluster region

C-Abl: gene for tyrosine kinase receptor

Bcr-c-abl gene for protein with increased tyrosine kinase activity


Which two regions are fused on the chimeric chromosome that causes Burkitt's Lymphoma?
What does each region do?

Immunoglobulin regulatory region
Myc: gene for transcription factor involved with cell proliferation, growth, angiogenesis


Briefly describe the tumour suppressing pathway

When mutations occur in the tumour suppressing pathway, genes that are normally involved with apoptosis and senescence are turned off. Cell don't die


Explain the Knudson Two Hit Model

Since we have two copies of each gene, it requires a mutation in both to cause cancer


What is it called when the second copy of the gene is mutated?

Loss of heterozygosity


What are the genetic mechanisms for loss of heterozygosity?

1. Non disjunction
b. followed by chromosome replication
2. Mitotic recombination
3. Deletion
4. Point mutation
5. Gene conversion


What does non-disjunction lead to?

Only one chromosome in the cell, only one copy of the gene


What does non-disjunction, then chromosome duplication lead to?

Two copies of the mutated gene


What does mitotic recombination lead to?

The mutated gene replaces the normal gene on the other chromosome


What does gene conversion lead to ?

Normal gene converted to the mutated one


How does deletion lead to L.O.H.?

Loss of the normal allele


How does point mutation lead to L.O.H.?

Loss of the normal allele


How can both genetic and epigenetic changes lead to L.O.H.?

Genetic: mutation in the normal allele

Epigenetic: silencing of the normal allele, so only the mutated one is active


What is p53?

This is a tumour suppressor gene
The mutated version is extremely common in cancers


What is normal function of p53?

It's a transcription factor -> binds to DNA and alters expression of genes

Normal function is cell cycle control
DNA repair
Genetic stability
Inhibition of angiogenesis


Where are most mutations of p53 localised?

In the DNA binding region of the transcription factor


What happens when p53 mutates?

When the gene for p53 mutates, the protein has a different DNA binding site
The transcription factor will bind differently to promoter regions


Explain Li-Fraumeni syndrome

This is a syndrome where people are born with one copy of a mutant allele of p53

This means they only have to receive one hit and they will develop the cancer


Does the p53 product undergo modifications?

Yes, post- translational


What are the hallmarks of cancer?

1. Uncontrolled cell proliferation
2. No cell death
3. Angiogenesis, blood supply to tumour
4. Avoids signals from growth repressors
5. Metastasis
6. Immortality


What is Myc?

This is a gene coding for a transcription factor that is involved with regulation of cell proliferation and angiogenesis


What is the structure of p53?



Describe the features of the loss of function mutations of p53

Some mutations of p53 are dominant negative
This means a single hit it sufficient to lose the tumour suppressor activity

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