case 4 - cancer

Question 1

what are the two classifications for cancer

Answer 1

familial cancers
sporadic cancers

Question 2

what are the features of familial cancers

Answer 2

1% of all cancers
Single gene mutations (Mendelian disorders)
Most are inherited as autosomal dominant traits
Most due to inherited mutations of tumour suppressor genes
Further genetic events are necessary if the mutation is in somatic cells. Even though the mutated gene is inherited, it isn’t sufficient for malignancy

Question 3

what are the features of sporadic cancers

Answer 3

99% of all cancers
Result of exposure to carcinogenic agents and unprepared DNA replication errors
Results in somatic activation/inactivation of cancer genes

Question 4

what type of onset is familial cancer

Answer 4

early onset

Question 5

what are the features of the cells in familial cancers

Answer 5

tumour cells - both copies of TSG inactivated

all other cells - one copy of TSG inactivated

Question 6

what is the onset of sporadic cancers

Answer 6

late onset

Question 7

what are the features of the cells in sproadic cancer

Answer 7

Tumour cells: both copies of tumour suppressor genes inactivated
All other cells: normal

Question 8

what is an adenoma

Answer 8

cancer of the glands

Question 9

what is a carcinoma

Answer 9

epithelial cells - 90% of all cancers

Question 10

what is a lymphoma

Answer 10

lymphocytes or lymphatic tissue

Question 11

what is a sarcoma

Answer 11

connective tissue

Question 12

what is a blastoma

Answer 12

immature / pre-cursor cells - dendrites - WBCs

Question 13

what is a papilloma

Answer 13

surface epthelial

Question 14

what are the two types of cancer genomic instability

Answer 14

Either chromosomal instability - result of many numerical and structural abnormalities

Or microsatellite instability - result of impaired DNA mismatch repair (MMR)

Question 15

what is telomerase

Answer 15

an enzyme that prevents the shortening of the telomere, thus preventing senescence

Question 16

what happens in normal cells

Answer 16

telomerase is switched off

Question 17

what happens in malignant cells

Answer 17

telomerase is switched on, thus inhibiting senescence

Question 18

what is sensence

Answer 18

specific number of cell divisions

Question 19

what does successful carcinogenesis require

Answer 19

either mutations that increase the rate of cell proliferation, so as to provide an expanded target for further mutations (clonal evolution)
or
mutations that destabilise the genome, so as to increase the rate of further mutations

Question 20

to be successful, what must a malignant cancer cell have

Answer 20

Become independent of external growth signals
Become insensitive to external anti growth signals
Become able to avoid apoptosis
Become capable of indefinite replication
Become capable of sustained angiogenesis
Become capable of tissue invasion and metastasis

Question 21

what is cancer mediated by

Answer 21

oncogenes and TSGs
telomeres
Wnt and Ras
CIN/MMR
p53 and apoptosis
cyclin,CDK, CDi

Question 22

features of (proto) oncogenes

Answer 22

gain of function
dominant - only need one mutated allele to be activated

Question 23

features of tumour suppressor genes

Answer 23

loss of function
recessive - need two mutated alleles to be inactivated

Question 24

what is a proto oncogene

Answer 24

is a normal gene that may be activated into an oncogene due to mutations or increased expression

Question 25

what do proto oncogenes promote

Answer 25

cell division, survival and growth

Question 26

what are the four ways in which proto oncogenes can be activated into oncogenes

Answer 26

Point mutations that increase protein function Gene amplification that causes over expression Chromosomal translocation e.g MYC Viral stimulation that may lead to addition/deletion of genes when viral DNA is integrated with human DNA

Question 27

what is MYC

Answer 27

it is a regulator gene that codes for a transcription factor. if translocated, MYC will continually be expressed, causing unregulated expression of many genes, some of which are involved in cell prolideration e.g cyclin D1 and result in the formation of cancer

Question 28

what is an oncogene

Answer 28

a gene that has the potential to cause cancer

Question 29

what are two examples of oncogenes

Answer 29

b catenin and KRAS

Question 30

what happens when one allele of oncogenes is mutated

Answer 30

there is a gain in protein function

Question 31

what do oncogenes usually code for

Answer 31

- Secreted growth factors (EGF, Wnt, Ras) - Cell surface receptors (HER) - Signal transduction system components (ABL) - Nuclear proteins transcription factors (MYC) - Cyclins/cyclin dependent kinases (Cyclin D1, CDK4)

Question 32

what are tumour supressor genes

Answer 32

body's natural defence mechanism against malignancy

Question 33

what happens when both alleles of TSGs are mutated

Answer 33

there is a loss of protein function

Question 34

what is inactivation of TSGs caused by

Answer 34

Mutations Chromosomal abnormalities Methylation of promoters Interaction with viral proteins

Question 35

what is worse, loss of TSG or activation of oncogenes

Answer 35

loss of TSG

Question 36

what is the function of tumour suppressor genes

Answer 36

inhibit progress through the cell cycle -CKi's - p21 promote apoptosis inhibit cell growth DNA repair cell adhesion to prevent metastasis

Question 37

all cancers metastisise except

Answer 37

glial cells of the CNS, these usually form benign tumours basal cell carcinomas of the skin

Question 38

what are the three pathways via which cancer spreads

Answer 38

direct seeing of body cavities or surfaces Lymphatic spread Hematogenous spread - blood