Unit 2- Overview of cancer and genetics

Question 1

What is cancer?

Answer 1

-Cells divide without stopping and spread into surrounding tissue
-Process of homeostasis broken down
>Old damaged cells survive without dying and new cells form when they are not needed… solid masses called tumours (except leukaemia cancer of the blood)

Question 2

What is malignant cancer? And the process of metastasis

Answer 2

-Tumours spread into nearby tissue
-Metastasis : Some cancer cells break off tumour and travel to distant places through blood or lymph and form new tumours far from the original.

Question 3

What is the nature of metastatic cancer?

Answer 3

-Same name and type of cancer cells as the primary cancer
-e.g. breast cancer spread to lung is metastatic breast cancer not lung cancer

Question 4

What is the difference between normal cells and cancer cells?

Answer 4

1. Cancer cells are less specialised than normal cells
   > undifferentiated
2. Ignore signals that tell cells to stop dividing or begin a process known as programmed cell death - apoptosis
3. Able to influence microenvironment which can feed tumour
4. Evade immune system and use it to stay alive and grow

Question 5

When is a tissue change cancer and when is it not cancer?

Answer 5

1. Hyperplasia :cells within tissue divide faster than normal - look and are organised normally
2. Dysplasia : build up of extra cells - look abnormal and are organised differently
3. Carcinoma in situ : Abnormal cells , organised differently. Sometimes called cancer but is NOT as cells :
   - do not spread beyond original tissue / or invade nearby tissue BM intact

Question 6

What is metaplasia?

Answer 6

-Transforms a cell from one form to another; caused by external stimulus; can be reversible; less likely to lead to cancer.

Question 7

How does cancer arise?

Answer 7

• Genetic disease
• Mutations to genes result in:
  1. Cells evade normal growth controls and become cancer
  2. Increase production of a protein that makes cells grow
  3. misshapen : non-functional form of a protein that normally repairs cellular damage

Question 8

What does it mean by a recessive or dominant mutation?

Answer 8

1. Recessive mutation to give rise to a mutant phenotype both alleles must cary the mutation
   -Inactivate the affected gene and lead to a loss of function
2. One copy of dominant mutant allele leads to mutant phenotype
   -Lead to a gain of function

Question 9

What are Germline mutations?

Answer 9

-Mutations in DNA that cause cancer can be inherited from parents if the changes are present in germ cells (eggs ad sperm)
-Germline mutations are found in every cell of the offspring

Question 10

What are Somatic mutations?

Answer 10

-Genetic changes that occur during a persons lifetime as a result of errors when:
> cells divide
> damage to DNA caused by environmental exposures e.g. Substances such as chemicals in tobacco and radiation such as UV rays from sun

Question 11

How does cancer vary within individuals?

Answer 11

• Everyones cancer has unique combination of genetic changes
• As cancer grows additional changes will occur
  -Within same tumour different cells may have different genetic changes

Question 12

What are the 3 drivers of cancer?

Answer 12

-Genes that contribute to cancer

1. Proto-oncogenes : Altered they may become oncogenes and allow cells to grow and survive when they shouldn’t (Dominant)
2. Tumour suppressor genes : Alterations cause cells to divide in an uncontrolled manner
3. DNA repair genes : fix DNA , causes cells with mutations in these genes to develop additional mutations in other genes. Together these mutations may cause the cell to be cancerous

Question 13

What do proto-oncogenes/oncogenes do?
(Gain of function mutation)

Answer 13

Proto-oncogene = A group of genes that cause normal cells to become cancerous when they are mutated
-stimulate cell division
-inhibit cell differentiation
-halt cell death
Processes necessary for normal human development

Oncogene=
> increase cell division
> decrease cell differentiation
> inhibit cell death

Question 14

What are the gain of function mutations that convert proto-oncogenes to oncogenes?

Answer 14

1. Point mutation: result in a continuously acting protein product
2. Gene amplification : Localised reduplication of a DNA segment that includes a proto-oncogene, leading to over expression of the encoded protein
3. Chromosome rearrangement: brings a growth regulatory gene under the control of a different promotor and that causes inappropriate expression of the gene

Question 15

What is important to note when it comes to gain of function mutations?

Answer 15

-Point mutations generate oncogene that encodes an oncoprotein that differs slightly from the normal protein encoded by the proto-oncogene.
-Gene amplification and chromosome rearrangement both generate oncogenes whose protein products are identical with the normal proteins; their oncogenic effect is due to their being expressed at a higher level than normal

Question 16

What do tumour-suppressor genes do?
(Loss of function mutation)

Answer 16

-Encode proteins that, when activated, inhibit cell proliferation
> if it is lost or mutated so that it loses its activity - Cell then uncontrollably divides, and this contributes to the development of cancer
>Both alleles must be mutated to promote cancer development

Question 17

How is cancer heredity or non-hereditary?

Answer 17

• Hereditary as : cells lack one of the two normal functional copies of tumour suppressor gene due to germline mutation
  >Tumours occur where the remaining copy is lost or inactivated by a somatic mutation

-Non - hereditary: Two functional copies of the gene
>Tumour rarises as both copies are lost or inactivated through the coincidence of two somatic mutations in a single line of cells

Question 18

What are the six ways of losing the remaining good copy of a tumour suppressor gene?

Answer 18

• Nondisjunction
• Nondisjunction and duplication
• Mitotic recombination
• Gene conversion
• Deletion
• Point mutation

Question 19

What are the five classes of proteins that are encoded by tumour-suppressor genes?

Answer 19

1. Intracellular proteins :Regulate or inhibit progression through a specific stage of the cell cycle
2. Receptors for secreted hormones : Inhibit cell proliferation
3. Checkpoint-control proteins : Arrest cell cycle if DNA is damaged or chromosomes are abnormal
4. Proteins that promote apoptosis
5. Enzymes that participate in DNA repair

Question 20

Why is a single mutation is not enough to change a normal cell into a cancer cell?

Answer 20

• If a single mutation was responsible for
  cancer, which has been occurring with a fixed probability per year, the chance of developing cancer in any given year of life should be independent of age.
• However the incidence for most types of cancer rises steeply with age
  > suggesting that cancer is caused by a progressive, random accumulation of a set of mutation in a single lineage of cells.

Question 21

What is tumour progression?

Answer 21

-An initial mild disorder of cell behaviour evolves into a full-blown cancer, due to gradual accumulation of mutations in a number of different genes

Question 22

What is the role of oncogenes and tumour suppressor genes in cancer development?

Answer 22

• The activation of oncogenes and the inactivation of tumour suppressor genes are critical steps in tumour initiation and progression.
• Accumulated damage to multiple genes eventually results in the increased proliferation, invasiveness, and metastatic potential that are characteristic of cancer cells.

Question 23

Compare 3 differences between benign and malignant cancer cells?

Answer 23

• Benign cells are monomorphic whereas malignant cells are pleomorphic
• Benign cells have reduced mitotic activity whereas malignant cells have high mitotic activity
• Benign cells have low nucleus to cytoplasm ration, malignant cells have high nucleus to cytoplasm ratio