Neoplastic Disease Intro Wk 4

Question 1

Outline the main principles of the Clonal Evolution and Cancer Stem Cell models of tumour formation, and explain their potential significance in relation to cancer treatment

Answer 1

Clonal: all cells in a tumour are of single origin, any cell is a target (random), driver cells can be propagated (have a growth advantage) daughter cells have compounding proliferation/driver advantage. All new driver mutations have potential to create tumours at different stages. Remove all.

Stem: Only stem cells can create tumours (are drivers). Growth advantages are limited to stemcells (decreased). Differentiation decreases proliferation. Can undergo symmetrical and asymmetrical cell division. Malignancy is still possible, though via a hierarchy model ie only stem cells can create new tumours. Remove only stem cells.

Question 2

Where to check for metastasizing cancer

Answer 2

Clinical diagnosis of metastasis in local lymph node.

Question 3

Explain malignant

Answer 3

Neoplasm ability to spread to surrounding tissue, blood, lymphatic tissue.

Question 4

Explain cancer

Answer 4

Malignant neoplasm

Question 5

Explain tumour

Answer 5

Swelling or mass, commonly all types of neoplasms.

Question 6

What is the order of cell differentiation from pluripotent to differentiated cell?

Answer 6

Pluripotent -> multipotent and oligopotent -> precursor -> differentiated.

Question 7

What is the order of cell differentiation and maturation from pluripotent to differentiated cell?

Answer 7

Pluripotent -> multipotent and oligopotent progenitor cells -> precursor -> differentiated.

Question 8

What changes in a cell as it matures and differentiates?

Answer 8

Cell phenotype: morphology, function and behaviour.

Question 9

What regulates cell phenotype?

Answer 9

Intrinsic and extrinsic factors

Question 10

How do intrinsic and extrinsic factors regulate cell phenotype?

Answer 10

Intrinsic: gene expression and protein function
Extrinsic: growth factors, signalling molecules

Question 11

How do intrinsic factors alter cell phenotype in neoplastic disease?

Answer 11

Abnormalities in genetic factors

Question 12

How do intrinsic and extrinsic factors regulate cell phenotype?

Answer 12

Intrinsic: gene expression and protein function
Extrinsic: growth factors, signalling molecules

Question 13

What is the 3-step process of how how a neoplastic disease occurs?

Answer 13

1. Multiple genetic and or epigenetic changes
2. Altered protein expression and or function
3. Altered cell function and behavior.

Question 14

What is the difference between driver and passenger genes?

Answer 14

Driver genes drive critical genes towards concern phenotype

Passenger genes are neutral to the process; and do not control (drive) the gene.

Question 15

How many driver genes need to be mutated to create a cancer cell?

Answer 15

Three to Seven genes

Question 16

What do genetic mutations and epigenetic changes cause?

Answer 16

Altered expressions of genes and their products, leading to loss or gain of cell function.

Question 17

What do mutations in genes cause?

Answer 17

Loss or gain of function of mutated protein products

Question 18

What is the affect of proteins with altered function?

Answer 18

Alters pathways and process in the cell, leading to phenotypic changes and the development of behaviours characteristic of cancer cells

Question 19

Do extrinsic factors contribute to the regulation of gene expression in neoplastic cells?

Answer 19

Yes. growth factors, signalling molecules

Question 20

What’re the six hallmarks of cancer?

Answer 20

1. Self-sufficient growth
2. Insensitivity to anti-growth signals
3. Evasion of apoptosis
4. Limitless replicative capacity
5. Sustained angiogenesis (growth of blood vessels into the tumour)
6. Tissue invasion & metastasis

Question 21

What are the genes which encode proteins which stimulate cell growth and division collectively called? What are they called when mutations occur in these genes?

Answer 21

Protooncogenes

Oncogenes [cancer causing genes]

Question 22

What are the genes which encode proteins such as growth factors which stimulate cell growth and division collectively called? What are they called when mutations occur in these genes?

Answer 22

Protooncogenes

Oncogenes [cancer causing genes]

Question 23

What are the name of the proteins and the genes which produce them called which function to inhibit progression through the cell cycle called?

Answer 23

Tumour suppressor proteins

Tumour suppressor genes

Question 24

What has to happen to chromosomal strands for a cell to undergo loss of function? How does this occur intrinsically and extrinsically?

Answer 24

The gene on both chromosomal strands (both alleles) needs to be inactivated (two hits). This occurs intrinsically by point mutations, rearrangements, insertions or deletions in the gene DNA sequence, or large deletions resulting in complete loss of the gene. Extrinsically, (epigenetically) a gene may be silenced due to methylation.

Question 25

What are a cancer cell’s behavioural changes?

Answer 25

Uncontrolled proliferation due to oncogene activation and tumour suppressor gene inactivation.

Avoidance of cell death, immortality and functional changes to facilitate invasion, metastatic spread and survival.

Question 26

What are three fundamental key points about tumour development?

Answer 26

1. Clonal origin
2. Heritable genetic/epigenetic changes alter cell behaviour.
3. Multistep process involving multiple hits affecting multiple driver genes