The non-inherited genome and cancer Flashcards
What is cancer and what causes it?
Cancer is the uncontrolled growth of abnormal cells in the body, caused by mutations that alter the function or regulation of genes involved in cell proliferation, cell death, (unregulation of mitosis and apoptosis), dna repair and other vital proccesses.
How can our genomes (that are relatively stable) acquire mutations over time?
Errors of replication or mutagenic agents
The vast majority of mutations that occur are what type?
Silent point mutations - little or no functional effect on genes they occur in - They are neutral because they do not change the amino acids in the proteins they encode.
What can a series of ongoing mutations lead to that will eventually result in cancer
An activating mutation of one of the two alleles of a proto-oncogene converts it to an oncogene, which can induce transformation in cultured cells or cancer in animals.
What is cellular transformation
the genetic alteration of a cell (normal cell transforms to cancer cell)
What is a passenger mutation?
a mutation that has no effect on the fitness of a clone but may be associated with a clonal expansion because it occurs in the same genome with a driver mutation.
What are cell numbers?
Product of the rates of cell division (mitosis) and cell death (apoptosis)
How are cell numbers regulated?
Controlling the rate of cell division and death of all cells within an organism
Why do cells die/produce constantly?
EXHAUSTION MOSTLY - cells don’t last very long as they undergo a tough job if we look at the functional gut cells - replaced so rapidly - gut exposed to a lot of stresses (toxins, food, ph changes) don’t last long! You are replaced - which is why you have a lot of mitosis in certain areas and then alot of apoptosis to balance.
How are new cells produced and how do old cells die?
New cells - precise duplication of contents of existing cell followed by cell division to form two daughter cells (mitosis)
Old cells - triggering a regulated cell death process known as apoptosis.
How can cancer be caused by this unregulation of cell numbers?
normal controls on processes that regultae cell numbers within tissues are lost.
Gene mutations - affect rate of mitosis and apoptosis and leads to accumulation of extra cells
How does cancer incidence vary between tissues?
Cancer’s are most common in epithelial cells than non epitehelial cells such as sacromas, blood-forming and CNS and PNS.
Is cancer a single disease?
No, it is a diverse group of conditions that all share a common increase in cell numbers within particular tissues.
Cancer can be split into two groups, what are they?
Benign (fail to spread to other tissues - non life threatening)
Malignant (cancer is invasive and spreads to other tissues within the body)
Cancers can arise from practically any tissue, but which tissue is the most common and why?
Epithelial -
1) highest risk of exposure to carcinogens because the cells line the surfaces of body that are in direct contact with environment (skin, lungs, mouth, stomach, intestine) and the environment is a major source of carcinogens.
2) epithelial cells are highly mitotic - have high replacement rate because they are prone to damage (exposure)
What is epithelial tissue?
sheets of cells that form the upper layer of skin and line the walls of cavities and tubes within the body
What are carcinomas?
cancers that arise from epithelia (these tumours are resp for 80% of all cancer-related deaths in western world)
What are tumours?
groups of abnormal cells that form lumps or growths (neoplasia)
When does a tumour become cancerous?
A tumour is cancerous when it: grows into nearby tissues (malignant), has cells that can break away and travel through the blood or lymphatic system and spread to lymph nodes and distant parts of the body.
Does cancer refer to a benign or malignant tumour?
Malignant
What are carcinogens and give examples?
A carcinogen is any agent that directly increases the incidence of cancer. Cancer causing agents - any substance, radionuclide, or radiation that promotes carcinogenesis, the formation of cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. chemical carcinogens (including those from biological sources), physical carcinogens, and oncogenic (cancer-causing) viruses.
Give an example of oncogenic viruses (carcinogen)
Examples include human papillomaviruses, the Epstein-Barr virus, and the hepatitis B virus, all of which have genomes made up of DNA. Human T-cell leukemia virus type I (HTLV-I), which is a retrovirus (a type of RNA virus), is linked to tumour formation in humans.
Give an example of physical carcinogens
Physical carcinogens include ultraviolet rays from sunlight and ionizing radiation from X-rays and from radioactive materials in industry and in the general environment.
Give examples of chemical carcinogens
inhaled asbestos, certain dioxins, and tobacco smoke.
Cancers arise more frequently in what type of tissues and why?
Highly mitotic - cells are already dividing at rel high rate and barriers to cell division are lower than in non dividing tissues (post-mitotic tissues)
Do all cells in the body divide at the same rate?
No, some exhibit low rates of cell division - brain and muscle tissue..heart (very stable - don’t hear much talk of cancer here.. may migrate there from other tissues)
Give examples of common cancers of epithelial origin
Adenocarcinoma - lung, colon, breast, esophagus
Squamous cell carcinoma - skin, lung, esophagus
What is adenocarcinoma and squamous cell carcinoma?
a malignant tumour formed from glandular structures in epithelial tissue, histolgoical type
originates from squamous cells
What does histological type mean?
type of tissue in which the cancer originates (histological type)
What are sarcomas?
Malignant tumours (cancers) that arise from non-epithelial tissues, arise from the various connective tissues (account for 1% tumours encountered in cancer clinics)
Give an example of sarcomas
Bone and soft tissue sarcomas are the main types of sarcoma. Soft tissue sarcomas can develop in soft tissues like fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues. They can be found in any part of the body
What are the three types of tissues that cancer can arise from?
Carcinomas - Epithelial
Sarcomas - Non-Epithelial
Blood forming (hematopoietic) tissues
Neuroectodermal tumours
What are heamtopoetic tissue cancers?
Blood-forming tissues and cells of the immune system
Give examples of hematopoietic malignancies
leukaemias and lymphomas (17% cancer related deaths)
What type of cancer causes the most deaths?
Carcinomas, then heamatopoetic, neuroectdermal tumours, then sarcomas
What are neuroectodermal tumours?
Tumours arise from various components of the central (.ie brain) and peripheral nervous systems (ie, spinal chord) and outlying nerve tissue (account for 17% cancer related deaths)
What is a mutation?
Alteration to the most commonly found coding sequence (wild type sequence) of a protein
Are all mutations bad?
Obviously not, we evolve because of mutations. Mutations can increase the activity of a protein or decrease it or generate the opposite function (some have no effect - silent).
How is a protein like a bike?
- proteins are comprised of different domains (sim to diff parts of bicycle) - some of which critical to function and others less
- if we have malfunctions (mutations) in some parts of bike, some would be critical while others would not (break bell or light - wouldn’t affect function, remove wheel or chain it would. puncture tyre - slow down bike but not cause it to stop functioning completely. removing brakes would not be immediate problem, lead to serious consequences in certain circumstances)
- THUS consequences of gene mutations can be serious, mild, or of little consequence depending on what part of protein is affected
Consequences of gene mutations can be serious, mild, or of little consequence depending on what?
what part of protein is affected
The types of mutations that can have diff consequences (serious, mild, no consequence) are what?
Loss-of-function mutations
Gain-of-function mutations
Dominant-interfering mutations (dominant-negative)
What are loss-of-function mutations?
Reduction in the function of the protein encoded by the gene which can be complete (complete loss of function, null mutation or knockout) or incomplete/partial (hypomorphic mutation)