Lecture 12- Cancer

Question 1

Clonal

Answer 1

• originated from a single common cell

- Primary and secondary tumors are clonal

Question 2

mutator phenotype

Answer 2

• what the high level of genomic instability in cancer cells is referred to
• in other words, it is the phenotype where cancer cells have a high level of genomic instability
• cancer cells have genetic defects that affect genomic stability, DNA repair, and chromatin modifications, and it is the defects/changes in these systems that lead to the mutator phenotype

Question 3

Changes/defects in which mechanisms lead to the mutator phenotype?

Answer 3

• Genomic stability
• DNA repair
• Chromatin modifications

Question 4

genomic instability

Answer 4

• can arise from translocations, aneuploidy, chromosome loss, DNA amplification, chromosome deletion, etc
• cancer cells have a LOT of genomic instability
• refers to a high frequency of mutation within the genome of a cellular lineage
• The cell doesn’t know how to grow or when to grow

Question 5

Philadelphia Chromosome

Answer 5

• A chromosomal defect that leads to cancer
• causes chronic myelogenous leukemia (CML)
• there is a translocation between Ch.22 and Ch.9 in which there is a fusion between the BCR gene and the ABL gene to form one giant bcr-abl fusion protein. This protein is overactive (by nature?) which causes the cascade to get constitutively turned on: bcr-abl causes tyrosine kinase to become constitutively turned on, tyrosine kinase then leads to to phosphorylation of multiple substrates, and this phosphorylation leads to genomic instability and less apoptosis, which leads to CML cancer

Question 6

ABL

Answer 6

• protein kinase that acts to produce growth in cells

- is fused to BCR in Philadelphia Chromosome

Question 7

xeroderma pigmentosum

Answer 7

• results from a defect in nucleotide excision repair

- is an example of a DNA repair defect (obv)

Question 8

Hereditary nonpolyposis colorectal cancer

Answer 8

• 4 genes in the mismatch repair are defective, so people with this have an increased risk of cancer in the colon, ovary, uterine, and kidney
• Is an example of DNA repair defect
• is autosomal dominant

Question 9

epigenetics

Answer 9

-study of factors that affect gene expression in an alterable way but do not affect DNA sequence

Question 10

cyclins

Answer 10

-a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinases. Different cyclins are present in different amounts at different stages of the cycle, and they are always at the same amount in the same stage each cycle. Mutations that cause this pattern to change can lead to a problem, which can lead to cancer

Question 11

What allows cancer cells to grow and proliferate?

Answer 11

• problems with the synthesis and correct amount of cyclins causes the regulation of the cell cycle to get violated, which can allow cancer cells to possibly breeze right through it
• Defects in the signal to induce apoptosis also allows the cancer cells to grow

Question 12

proto-oncogene

Answer 12

• a normal gene that, when altered by a mutation, can become an oncogene which can contribute to cancer
• Examples of proto-oncogenes include TXN factors that stimulate the expression of genes, signal transduction molecules that stimulate cell division, and cell cycle regulators that move cells through the cell cycle
• In normal cells the proto-oncogenes are quiet and “turned off” when the cell stops dividing, so it is regulated
• in cancer cells, it is unregulated, making it an oncogene, and the mutate is constitutively ON

Question 13

oncogene

Answer 13

• An unregulated proto-oncogene in which the gene is constitutively ON, which can lead to cancer
• The formation of oncogenes is a gain of function mutation, since oncogenes are literally just proto-oncogenes that are more active
• are associated with the G0 signal the allows the cell to keep going through the cell cycle

Question 14

apoptosis

Answer 14

-programmed cell death

Question 15

tumor suppressor

Answer 15

• regulates cell cycle checkpoints and apoptosis; can put the brakes on the cell cycle if a problem is sensed.
• In cancer cells, tumor suppressors are mutated or inactivated so they can’t work as well, which can allow mutation to slip through, and can lead to more mutations being produced and getting through
• inactivation of tumor suppressor is a loss of function mutation
• are associated with the STOP signal in the cell cycle

Question 16

Ras proto-oncogene

Answer 16

• ras is early on in the pathway that can lead to transcription factors that can activate or repress gene activity
• they are controlled by growth factors, and alternate between being off or on based on the presence of their growth factor
  some of the most frequently mutated genes in human tumors are ras proto-oncogenes
• about 30% of tumors have ras mutations

Question 17

p53 tumor suppressor gene

Answer 17

• is the most common mutated gene in human cancer: is found in 50% of human cancers
• p53 is a transcription factor that initiates either apoptosis or cell cycle arrest, which are both able to block cancer development

Question 18

RB1 tumor suppressor gene

Answer 18

• loss of function of this gene contributes to many cancers, but it is recessive? b/c you need to knockout both copies to get the uncontrolled growth.
• one knockout can be inherited, in which case these individuals only need one more “hit” to get the uncontrolled growth. I would assume this “hit” would need to be the knockout in the other copy.
• These individuals who inherit a knockout have an 85% chance of developing cancer
• The transcription factor that controls the transcription of RB1, E2F is inactive when bound to pRB. Cyclin D1 phosphorylates pRB which makes it release E2F so it can allow RB1 to be transcribed

Question 19

metastasis

Answer 19

• spread from an initial site to another site; the development of malignant growth at another site aside from where it originated
• occurs by a cancer cell traveling through the body and taking root somewhere else