aging and disease lecture 4- cancer 1

Question 1

what is cancer?

Answer 1

when abnormal cells divide in an uncontrolled way. some cancers may eventually invade surrounding cells and they are all genetic diseases

Question 2

what are the most common cancers? (more than half cases)

Answer 2

-breast
-prostate
-lung
-bowel

Question 3

when is the highest age range for cancer?

Answer 3

85-89, it reaches a peak at this age for incidence and then it willl decrease over 90

Question 4

is cancer a genetic disease?

Answer 4

yes, the susceptibility to some cancers is familial. most common mutations are found in cancer

Question 5

how many independent mutations are required?

Answer 5

5-6

Question 6

what are germline mutations?

Answer 6

passed from parent through egg or sperm and goes to all cells in the affected offspring, making it heritable which cause cancer family syndromes

Question 7

what are somatic mutations?

Answer 7

a somatic mutation occur in non-germline tissues, making them nonheritable

Question 8

what are proto-oncogenes?

Answer 8

genes that encode proteins that stimulate cell proliferation. they are normal cellular gene usually involved in cell growth or cell division

Question 9

what are tumour suppressor genes?

Answer 9

genes that encode proteins that prevent cell proliferation

Question 10

what are oncogenes?

Answer 10

a proto-oncogene that has been activated by mutation or over expression. results in a dominant gain of function phenotype, only one copy to be mutated

Question 11

what is a point mutation?

Answer 11

can convert proto-oncogenes into oncogenes by deletion or point mutation in coding sequence. this results in a hyperactive protein made in normal amounts = uncontrolled growth = cancer

Question 12

what is gene amplification?

Answer 12

convert proto-oncogenes into oncogene by having extra copies of genes being copied. there is normal protein activity but in large volumes

Question 13

what is chromosomal rearrangement?

Answer 13

can convert proto-oncogenes into oncogenes by crossing over genes resulting in over production of normal genes or a greatly overproduction of fusion protein

Question 14

what must a mutation be?

Answer 14

loss of function and recessive so both copies are needed to be mutated

Question 15

how does a tumour suppressor lose its function?

Answer 15

normally these genes suppress cell division but a mutation causes them to lose their function

Question 16

what are the 2 types of cancer in knudsons 2 hit hypothesis?

Answer 16

sporadic (no hereditary) and familial (hereditary)

Two mutations (two-hits) are required for loss of tumour suppressor function
The first “hit” is inherited & the second “hit” is somatic

Question 17

what is retinoblastoma?

Answer 17

the loss of a single gene (Rb) is a key step in developing a tumour of the retina

Question 18

what happens when non-phosphorylated Rb bound to E2F gets phosphorylated?

Answer 18

-PhosphorylatedRb releases E2F.
-E2F migrates to the nucleus to induce transcription
-Proteins required for cell cycle progression

Question 19

what is sporadic retinoblastoma?

Answer 19

60% of retinoblastoma cases
Develops in children with no family history
Occurs in one eye

Somatic mutation in one allele
Somatic mutation in other allele
causing single tumour …

Question 20

what is hereditary retinoblastoma?

Answer 20

40% of retinoblastoma cases
Onset typically earlier than sporadic cases
Multiple tumours involving both eyes
Consistent pedigrees; siblings and offspring develop the same type of tumours

Tumour suppressor gene containing a germline mutation in one allele – heterozygous for the mutation
then a Somatic mutation in other allele
which leads to multiple tumours

Question 21

what is p53?

Answer 21

-p53 is a transcription factor that regulates the cell cycle, DNA repair and apoptosis
-Is a tumour suppressor gene
-Mutations in p53 are implicated in ~50% of human cancers, including cancers of the breast, lung, colorectal and stomach.

Question 22

why is there no homozygous. Rb mutants?

Answer 22

homozygous Rb mutants – embryonic lethal

Question 23

what happens during a norma cell cycle in response to dna?

Answer 23

Tumour suppressors function in many key cellular processes including the regulation of transcription, DNA repair and cell:cell communication.

The loss of function of these genes leads to abnormal cellular behaviour.

Question 24

what happens in the absence of p53?

Answer 24

cell cycle is not inhibited and increased cell division occurs

Question 25

what are breast cancer stats?

Answer 25

-15% of cancer cases are breast
-peak age is 90+

Question 26

where does breast cancer occur?

Answer 26

breast cancer occurs in the cells that line the lobules that manufacture milk or more commonly in the ducts that carry it to the nipple.

Question 27

what mutation causes most hereditary cases?

Answer 27

BRCA1 and BRC12 mutations. most are causes by sporadic except around 7-10% and BRCA1 is majority cause out that percentage

Question 28

what do these mutations cause?

Answer 28

-an increase in risk of early onset of breast cancer

Question 29

what are sporadical and hereditary mutations in breast cancer?

Answer 29

SPORADIC breast cancer:
Older women
One tumour
One breast (unilateral)

FAMILIAL (BRCA1 mutation: heterozygous)
Younger women
Often multiple tumours
Often affects both breasts (bilateral)

Question 30

what is the function of BRCA1?

Answer 30

BRCA1 protein REQUIRED for normal DNA repair

Loss-of-function:
( up to ~300,000 mutations per cell division)

so losss of function causes an accumulation of mutations= cancer

Question 31

what is number ~250?

Answer 31

Only a subset mutated in any given cancer type or individual tumour

Question 32

what is a growth factor?

Answer 32

induces cell proliferation
eg PDGF

Question 33

what is a receipt tyrosine kinase?

Answer 33

Transduce signals for cell proliferation
eg egfr

Question 34

what are transcription factors?

Answer 34

Regulate transcription of genes that induce cell proliferation
eg Myc

Question 34

what is signal transducing proteins?

Answer 34

involved in signalling eg Was