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Lecture 11

Lecture #11- Genetics of cancer

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University of Toronto St. George
Human Biology
Michelle French

Lecture 11 -To get a sense of the questions that are going to be on the midterm, go on the library website and access the past exams. The past exams are most representative of the questions that will be on the upcoming test. -The genetics of cancers ties together the topics of mutations that weve been talking about for a while. -There are over one hundred types of cancers in which cells can grow out of control & destroy healthy tissue. The kinds of things that can happen are there is a failure to regulate growth, proliferation, and/or cell death. Cell death is when cells die. Usually, theyll die if theyve been injured in some fashion. -The overall cause of cancer, from a biological point of view, is mutations in genes. These mutations can result in some instanc es in altered gene expression. -These are some of the characteristics of a cancer cell. -Most normal cells will, when you put them in a culture dish, will divide until they reach the edge of the dish and the dish is completely full of cells but the cel ls do not have the abi l iyt to grow over one another. So a normal cell would have this characteristic called contact inhibition. When the cells are contacting other cells, they stop growing. Thats absent in cancerous cells where they continue to proliferate even when theyre touching other cells. -When you damage normal cells, so say you damage DNA by irradiating it, it will usually die via cell death. In some instances, the cancer cells are resistant to radiation they remain alive even in the presence of radiation. This isnt the case for all cancer cells since radiation is used to treat certain forms of cancer. -As well, theres genomic instability. If you look at the karyotype (a picture of the chromosomes) of a cancerous tumour, youll often see huge changes in the chromosome number, translocations, etc. Part of the reason is that throughout the cancer process, theres a defect in repair. So that can also be part of a cancer process where you end up w/ even more mutations than previously. -Some cancers are immortal in the sense that in normal cells, you can grow cells for a certain period of time and then they die whereas certain cancer cells can continue to grow for many years. -There are cells used in labs called HeLa cells which came from a woman w/ cervical cancer in the 40s or 50s and her cells are still being cultured today in labs. So these cells have become immortal. -Tumour cells have the ability to break through tissues and basement membranes and move to other locations. This process is called metastasizing which is the ability to move to a new place. So they can go and disrupt local tissues, move through the blood, and move into different locations. This is only characteristic of some cancers. -This is a model of how cancer developed. -The idea is that there are several mutations that have to happen in different genes before a cell becomes cancerous. For example, so there has to be a 1 mutation in a gene, a 2 mutation in a different gene, a 3 rd mutation, and finally, by the time you get a 4 mutation, you have a malignant cell. -As you get older, your chance of developing cancer increases. So presumably, some of the cells in your body have lived longer and have been exposed to different incidents for a longer period of time and had the chance to build up mutations. -The incidence of cancer in males increases with age. -Over a lifetime, a cell will develop more mutations b/c theres been more chance/time to develop mutations. -As well its possible to isolate cancer at different stages of the development of cancers. So youve probably heard of the idea that a tumour being benign & then getting more and more cancerous & then eventually becoming malignant and having the ability to metastasize. -So scientists actually took out little growths that represent early stages of cancer and later stages of cancer for a variety of body parts and they discovered that the number of mutations in the small polyps (small growths) is small in comparison to the number of mutations in the genes that you see in a more malignant cell. -This reinforces the evidence for the multi-hit model of cancer development. -Theres also a concept that it only takes a single cell to have these several mutations for the cancer to develop. -Best evidence for this idea comes from females where you take out a tumour from a female. All areas whether its a tumour or another part of the body thats normal, if you look at those cells, remember that they will have a random X inactivation. So in a patch of normal tissue, you would expect to see cells that have 1 X inactivated and other cells the other X inactivated. -Thats what you would observe in a tissue sample if you had a way to distinguish b/w the 2 X chromosomes to see which one was active say by looking at specific types of enzymes thats coded by the X chromosome then youd see 2 differences representing the paternal or maternal enzyme form. -In the case of tumour cells however, you would only get the 1 form of the enzyme which represents the fact that in each of the cells of the tumour, the same X is inactivated. This suggests that a single cell w/ a certain X that was inactivated gave rise to the entire tumour. And that single cell acquired several mutations as it became a tumour. -This is called a clonal expansion of 1 cell during the development of cancer. effects that are known to cause cancers are called environmental mutagens. They include UV light, X-rays, chemicals, and others that are known to cause damage to the DNA resulting in mutations which leads to cancer. -Theres a combination of environment plus genes that influence cancer development. -As well, you might be extremely unlucky & inherit a gene that will make you more susceptible to cancer development. There is a component of development of cancer thats inherited & in that instance, youre inheriting a mutated version of the gene that will make you more susceptible. -In different populations and in different countries, you have different incidences of common cancers. This would be partly genetics as well as partly environment that influences the type of cancer that individuals develop. -Dont need to memorize this, just known the main idea. -Asbestos and cigarette tars are linked to lung cancer. -HPV causes cervical cancer and it is now something that can be vaccinated against to reduce the risk of developing cervical cancer. -Certain types of behaviour (e.g, smoking) increases the likelihood of developing cancer. -Females tend to lag behind the males b/c females didnt take up smoking as quickly as males too
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