14.1-14.2 Cancer is a genetic disease Flashcards
What is cancer?
When cells have lost the normal control of cell division and cell growth becomes unregulated
Which are the most commonly diagnosed cancers in the world?
- Lung
- Breast
- Colorectal
- Stomach
- Prostate
Where in the world are cancer deaths more likely to occur?
Less developed countries
What is cancer caused by?
Mutations in DNA that alter the way a gene functions and allow a cell to grow, multiply and spread in an abnormal way
What is a somatic mutation?
Somatic mutations affect a particular tissue and are heritable.
What are susceptibility genes?
Some people are born with genes that give them an increased susceptibility to cancer
Where do most mutations arise from?
Environment and lifestyle
How many genes are in the human genome and how many are known to contribute to the progression of cancer?
Between 20,000 to 25,000 genes in genome
Over 400 know to contribute to cancer
Broadly, how many types of cancer genes are there?
4
What is an oncogene?
A gene that has the potential to cause cancer
What are proto-oncogenes in normal cells?
Genes that help promote cell growth. Apart from when a cells needs to grow and divide, these genes are normally switched off and are not active
What happens to proto-oncogenes in cancer cells?
Changes or mutations in a proto-oncogene can switch the gene on, causing it to become an oncogene, which signals the cell to grow and divide into a tumour
What happens to proto-oncogenes in cancer cells?
Changes or mutations in a proto-oncogene can switch the gene on, causing it to become an oncogene, which signals the cell to grow and divide into a tumour
What is a tumour suppressor gene in normal cells?
In normal cells, tumour suppressor genes actively prevent cell growth
What is a tumour suppressor gene in cancer cells?
When mutated, these genes no longer stop a cell from growing
Which tumour suppressor gene is most commonly defective in human tumour cells?
p53
What are DNA repair genes in normal cells?
Repair and maintain DNA and correct errors
What are DNA repair genes in cancer cells?
Mutations in oncogenes and tumour suppressor genes are not repaired, driving cancer progression
What are apoptosis genes?
Faulty cells usually self-destruct through apoptosis to prevent cancer cells from forming. If they become mutated, a faulty cell can survive and grow into cancer
What is a DNA sequence mutation?
Changes to the sequence of nucleotides in DNA
What are the 4 types of DNA sequence mutation?
- Substitution of one nucleotide for another
- Insertion of extra nucleotide(s)
- A deletion of nucleotide(s)
- A frameshift whereby a deletion or insertion shifts the way the DNA sequence is read
What is a translocation mutation?
Movements of large amounts of DNA, often at the level of the chromosome, to a different chromosome
What is gene amplification?
Production of too many copies of a gene or set of genes at one location on a chromosome
What are inversions?
When a piece of DNA breaks away from a chromosome and is then reinserted in the opposite orientation
What are duplications/deletions?
Where a gene or groups of genes may be copied more than once on a chromosome, or lost completely
What is aneuploidy?
Gain or loss of a chromosome(s)
What are epigenetic changes?
Changes to the DNA that do not change the sequence
Which types of mutation are characteristic of solid tumours?
Point mutations, insertions/deletion and amplifications, and often aneuploidy
Which types of mutation are characteristic of haematological malignancies?
Specific chromosome rearrangements e.g. 9,22 translocation in CML
What are the phases of the cell cycle?
G1 - cell increases in size and prepares for DNA synthesis
S - DNA replication occurs
G2 - cell continues to grow and prepares to enter M (mitosis) phase and divide
M - cell growth stops and cell undergoes division into two daughter cells
G0 - resting phase
What are the 8 hallmarks of cancer?
- Cancer cells continue to grow
- Ignore programs to stop growth
- Evasion of immune system
- Invasion and metastasia
- Immortality
- Angiogenesis
- Deregulation of energy supplies
- Resist cell death
Describe ‘cancer cells continue to grow’
Growth promoting signals are disrupted allowing the cell to divide and grow continuously
Describe ‘cancer cells ignore programs to stop growth’
Tumour cells evolve a variety of strategies to ignore inhibitory signals and continue to grow and divide
Describe ‘evasion of immune system’
Cancer cells avoid detection by tumour immune-surveillance and evade eradication by the immune system
What cells are involved in immune-surveillance and what do they release?
T-lymphocytes, which release cytokines, which activate other T-cells and other immune cells
What are some examples of cytokines and what can they be used for?
Interferon (IFN), interleukin-2 (IL-2), tumour necrosis factor (TNF). Some cytokines can be used as anti-cancer therapy for some types of cancer
Who can be at greater risk of developing cancer?
Someone with a depressed immune system (e.g. elderly or those with AIDS)
What mechanisms can cancer cells use to evade the immune system?
- Lack the proteins that the immune system uses to recognise them
- Fail to activate a T-cell response
- Release substances that block immunosurveillance
- Grow so fast that the immune system is overloaded
Describe ‘invasion and metastasis’
Cancer cells can acquire the ability to invade adjacent tissue and travel to the blood or lymphatic system to spread to other organs in the body (metastasis)
Describe ‘immortality’
Cancer cells can exhibit unlimited replication potential and become immortal
Describe ‘angiogenesis’
Tumours require nutrients, oxygen and an ability to eliminate waste. Tumours can develop new blood vessels by angiogenesis to address these needs. Newer cancer treatments target this
Describe ‘angiogenesis’
Tumours require nutrients, oxygen and an ability to eliminate waste. Tumours can develop new blood vessels by angiogenesis to address these needs. Newer cancer treatments target this
Describe ‘deregulation of energy supplies’`
Major reprogramming of cellular energy metabolism is required to support the continuous cell growth and proliferation of cancer cells
Describe ‘resist cell death’
Cancer cells can bypass apoptosis, enabling the abnormal cells to continue to grow
Describe the multi-step process of cancer
- Cell experiences a mutation that makes the cell more likely to divide that it normally would
- The altered cell and its descendants grow and divide too often (hyperplasia). At some point, one of these cells experiences another mutation that further increases its tendency to divide
- This cell’s descendants divide excessively and look abnormal (dysplasia). As time passes, one of the cells experiences yet another mutation
- The cell and its descendants look abnormal in both growth and appearance. If the tumour that has formed from these cells is still contained within its tissue of origin, it is called in situ cancer
- If some cells experience additional mutations that allow the tumour to invade neighbouring tissues and shed cells into the blood or lymph, the tumour is malignant. The escaped cells may establish new tumours (metastases) at other locations in the body
Why do people die from cancer?
Metastatic disease
What is metastasis?
Tumour cells detach from the original primary tumour, invade nearby tissue and are carried through the bloodstream or lymphatic system to other parts of the body and start growing there
What is intercellular adhesion?
Normal cells are held together by a network of proteins (extracellular matrix). Cells keep their position in the matrix by cell-to-cell adhesion
How can cancer cells spread around the body?
Cancer cells can avoid intercellular adhesion and detach themselves from the extracellular matrix without dying. They may do so because they lack the adhesion molecules, or because they secrete enzymes that digest the matrix
What happens when cancer cells invade the lymphatic system?
They can pass into the lymph nodes and become stuck there. The majority are killed by resident immune cells, but some survive and grow to form tumours
What happens to cancer cells that get into the bloodstream?
They can become lodged in a capillary network as they are transported around the body. The majority of cancer cells will not survive this journey, but the ones that do can form a secondary tumour in the adjacent tissue
