Cancer cell biology 1

Question 1

what is the difference between a benign and malignant tumor?

Answer 1

benign= localized growth, grow by expansion, compression, or displacing surrounding normal tissue

malignang = capable of invasion or metastasis, grow by local inflitration, destroying the tissue through which they invade

Question 2

what do carcinomas, sarcomasl and leukaemias derive from?

Answer 2

1. carcinomas= arise from epithelial cells
2. sarcomas= arise from mesodermal origin (muscle, bone, fibroblasts)
3. lymphoma/leukaemia = develop from circulating cells of blood and lymph systems

Question 3

what two models exist to account for the heterogeneity and differences in tumour regenerative capacity?

Answer 3

1. clonal evolution model = mutant tumour cells with a growth advantage are seleceted and expanded
2. cancer stem cell model - refers to a rare subset of tumour cells that have the ability to self-renew and generate diverse tumour cells

*these models aren’t mutually exclusive - cancer stem cells can undergo clonal evolution

Question 4

describe in detail the cancer stem cell model

Answer 4

• tumours are functionally heterogenous and hierarchical
• tumours composed of cells that can initiate tumours (cancer stem cells) - and cells that arise from these cells, but cannot initiate tumours
• very low frequency of tumour stem cells within the tumour
• this has implications on cancer treatment b/c the old treatment killed anything rapidly proliferating (which would be the cells that arise from stem cells ) but it doesn’t kill the stem cells themselves (which means they can initiate another tumour potentially)

Question 6

mutations in what three classes of genes can cause cancer?

Answer 6

1. proto-oncogenes
2. tumour suppressor genes
3. care taker genes

Question 7

what is the normal activity of proto-oncogenes?

Answer 7

normally, they promote cell proliferation

mutant forms = oncogenes

when mutated, they create forms that are excessively active

Question 8

what is the normal activity of the tumour supressor gene?

Answer 8

they normally inhibit cell proliferation or promote apoptosis - normally for these genes you need to see a mutation in both allels for these genes to be effected

Question 9

What is the normal function of care-taker genes?

Answer 9

they are the ‘car maintenance check’s = they ensure accurate replication, repair, and segregation of DNA - mutations in these can lead to genomic instability

Question 10

what are the 6 biological capabilities acquired during the multistep development of human tumours? *the hallmarks of cancer

Answer 10

1. sustaining proliferative signaling
2. evading growth suppressors
3. activating invasion and metastasis
4. enabling replicative immorality
5. inducing angiogenesis
6. resisting cell death

Question 11

how can tumour suppressor genes be inactivated?

Answer 11

1. deletion (loss of functional gene copy leads to loss of heterozygosity)
2. point mutation
3. methylation of promoter- transcriptional silencing - methylation blocks the transcription factor from binding = silencing mutation
4. miRNAs- post transcriptional silencing

Question 12

what is a ‘nonsense’ mutation

Answer 12

a mutation that indicates an innapropriate ‘stop’ codone

Question 13

what is a conservative or non-conservative missense mutation?

Answer 13

conservative = codes a different nucleic acid sequence, but ultimately is translated into the same AA

non-conserative= codes for a different nucleic acid sequence and is translated, consequently, into a different AA

Question 14

give four examples of tumour suppressor genes

Answer 14

• RB
• P53
• APC
• BRCA1

Question 15

what are the normal functions of the Proto-oncogenes?

Answer 15

• growth factors
• cell surface receptors
• intracellular signal transduction molecules
• DNA binding proteins
• cell cycle proteins - cyclins, cdks, kinase inhibitors, apoptosis inhibitors

Question 16

what are the three ways proto-oncogenes can be activated?

Answer 16

1. point mutation or deletion - Ras , EGFR
2. gene amplification - MYCN
3. chromosome rearrangement - BCR - ABL

Question 17

describe the RAS oncogene control system

Answer 17

RAS is mutated in 20-30% of cancers

• “off” RAS is bound to nucleotide guanosine diphosphate
• “on” state RAS is bound to guanosine triphosphate
• mutated RAS revents GTP hydrolysis to GDP so constitutively active

Question 18

describe the oncogene activation by deletion and EGFR implications?

Answer 18

EGFR requires binding of epidermal growth factor (EGF) to enable kinase activity

the catalytic domain then transfers phosphate groups to target proteins to activate them - leads to translation of proteins involved in mitosis

oncogenic form of EGFR produces a receptor that doesn’t require EGF binding and is furthermore always “active”

the oncogene produce is capable of activating the pro-growth pathway in the absense of pro-growth signals

Question 19

describe oncogene activation by gene amplification and it’s implications on MYCN in neuroblastoma

Answer 19

MYCN is an oncogenic transcription factor that alters expression of hundreds of genes- MYCN amplification is marker of poor prognosis in patients with neuroblastoma *we use it to determine optimal therapy*

Question 20

Describe oncogene activation by chromosome rearrangment

Answer 20

translocation of an enhancer to a region that is normally silenced -

Question 21

what is microsatellite instability?

Answer 21

DNA level instability underlying DNA mismatch repaire defects

Question 22

what is chromosomal instability?

Answer 22

abnormal karyotypes = extra/missing chromosomes, chromosome rearrangments

Question 23

what is the relationship between telomerase and cancer?

Answer 23

cancer cells avoid apoptosis or senescence by activating telomerase - which adds repeats back on the ends of chromosomes