Neoplasia 2 Flashcards Preview

Jason's Respiratory Block > Neoplasia 2 > Flashcards

Flashcards in Neoplasia 2 Deck (65):
1

What would you target to control cell survival, growth and differentiation?

signalling pathways

2

4 emerging hallmarks in cancer replication?

deregulating cellular energetics
immune evasion
tumor-promoting inflammation
genome instability/mutation

3

4 classes of normal regulatory genes?

proto-oncogenes
tumour suppressor genes
apoptosis genes
DNA repair genes

4

Example of DNA repair genes defective?

BRCA1, BRCA2

5

how would aberrant DNA repair lead to cancer?

rapid accumulation of mutations in 'hotspot' oncogenes/TSGs

6

Her2-neu, Ras, Myc are examples of?

oncogenes

7

P53, Rb, APC, PTEN are examples of?

TSGs

8

How many alleles need to be lost to lose TSG function?

2

9

How many alleles of oncogenes need to be activated/mutated?

1

10

Types of gene mutations in cancer? 4 types

errors in DNA repair
point mutations in onco/TSGs
amplification of oncogenes
chromosomal rearragements

11

Difference between mutation and polymorphism?

mutation: any change away from what is defined as 'normal'
polymorphism: variation that is common in population (no sequence is 'normal')

12

Common amplifications/mutation in cancer?

TP53
PIK3CA
PTEN
RB1
KRAS

13

What is RB gene mutation responsible for?

retinoblastoma

14

What are?
TP53
PIK3CA
PTEN
RB1
KRAS

Common amplifications/mutation in cancer

15

oncogenes affect 5 categories of growth:

growth factors
growth receptors
protein signal transduction
nuclear-reg proteins
cell-cycle regulators

16

What is SNP in cancer?

single nucleotide polymorphism

17

polymorphisms in cancer depends how on SNPs?

how they are expressed, the alterations could change stability, influence risk

18

Oncogene amplification and overexpression are synonymous?

Nope. Amplification is more copies of a gene

19

What are double minutes in neoplasia?

extra chromosomes containing only oncogenes. holy shit.

20

Gene translocations and fusions make what?

novel hybrid genes that affect signaling pathway

21

BCR-ABL hybrid gene affects what?

tyrosine kinase

22

What must you consider re: neoplastic growth?

rate at which tumor cells are shed or die or differentiate

23

what happens to the proportion of cells in growth fraction as it grows?

growth fraction declines

24

Example of high growth fraction tumours?

leukemias, lmphomas, small-cell carcinoa

25

example of low growth fraction tumours

breast, colon

26

low growth fraction tumours production vs. death are simliar? or different?

similar. production is 10% greater than loss

27

doubling time f clinically detectable colon or lung tumours is how long?

2-3 months

28

Pten blocks THIS important kinase

PI3 kinase (growth pathway)

29

What are proto-oncogenes?

normal cell proliferation genes

30

What are oncoproteins?

proteins that come from oncogenes

31

In oncogenesis, what happens with growth factors?

autocrine loops

32

In oncogenesis, what happens with growth factor receptors?

over expression/active

33

In oncogenesis, what happens with cyclins/CDKs

uncontroled cell cycle progression

34

RAS Oncogenes (H-Ras & K-Ras), what happens in mutant RAS?

the negative feedback(GTP hydrolysis) of active RAS to inactive RAS is broken

35

What are P54 and RB?

TSGs that regulate cell cycle directly

36

Pten inhibits what?

oncogenic pathway of PI3 kinase

37

How do you get loss of heterozygosity in neoplasm?

Both TSG genes lost

38

how are familial predisposition and TSGs involved?

inherit one defective gene, lose the other one via mutation, or could lose both on an unlucky fluke

39

What the only cancer that only needs one gene mutation to activate?

retinoblastoma

40

prevalance of retinoblastoma?

1/20000

41

treatment for retinoblastoma?

enucleation

42

Rb causative factor only in eye?

Nope, features in many tumour types

43

define loss of heterozygosity (LOH)

loss of normal function of one allele where the other one was already inactivated.

44

What is Knudson's "two hit" hypothesis for LOH?

generation one has one RB allele gone, their kids all have one already gone so all it takes is another one to go before you get tumours

45

What is the guardian of the genome?

p53

46

what is p53?

transcription factor that can regulate expression of cell cycle factors

47

p53 helps out a lot with what cellular response to damage?

apoptosis directing

48

What is miRNA?

microRNAs, non-coding single stranded that function as negative regulators of genes

49

about how many nucleotides are miRNA?

22

50

How would miRNA affect oncogenes?

not enough expressed leads to too much oncoproteins

51

How would miRNA affect TSGs?

too many miRNAs leads to too little tumour suppresor proteins

52

What does methylation around TSGs do?

inactivated them

53

epigenetic control of TSG expression is heritable?

yes

54

pRB checkpoints which part of cell cycle?

end of G1

55

p53 checkpoints which part of cell cycle?

S-phase

56

6 ways to evade apoptosis

1. reduce CD95
2. inactivate death signal via FLICE
3. upregulare BCL2
4. reduce BAX cause of loss of p53
5. loss of APAF-1
6. upregulation of apoptosis inhibitors

57

What happens with telomeres and cancer?

tumour cells reactivate telomerase and achieve immortality

58

4 steps for tumour to become metastatic:

1. detachment of cells from each other
2. degradation of ECM
3. attach to novel ECM areas
4. migration

59

what cellular glues are disrupted in metastasis? 3 of them

cadherins
beta-catenin
connexins

60

are adherance molecules affected in cancer signalling pathways?

yes

61

What are popular angiogenesis targets for therapeutics?

VEGFs
VEGF-Rs

62

Explain tumour heterogeneity.

every tumour is different from it's primary tumour and every region within the same tumour can be different

63

what is a tumour initiating cell?

human tumour growing in mouse when transplanted

64

What are cancer stem cells?

arise from adult stem cells, intrinsic resistance to conventional therapies

65

Why are cancer stem cells, intrinsic resistance to conventional therapies?

conventional therapy doesn't kill the original cell so it relapses easily