93 -Neoplasia 2

Question 1

Emerging hallmarks of cancers
1
2
3
4

Answer 1

Avoiding immune destruction
Tumour promoting inflammation
Genome instability and mutation
Deregulating cellular energetics

Question 2

Pattern of mutations in cancer cells

Answer 2

Often a collection of small mutations over time which lead to malignancy.

Question 3

Pattern of mutations in cancer cells

Answer 3

Often a collection of small mutations over time which lead to malignancy.

Question 4

Aetiology of colon cancer
1
2
3
4

Answer 4

1) Normal mucosa (germline mutation may or may not be present, might acquire mutation - first hit)
2) Mucosa at risk (Methylation abnormalities, inactivation of normal alleles - second hit)
3) Protooncogene mutations, loss of additional cancer suppressor genes (adenoma)
4) Additional mutation, gross chromosomal alterations (carcinoma)

Question 5

Four classes of normal regulatory genes that are principal targets of genetic damage relevant to carcinogenesis

Answer 5

• Growth-promoting proto-oncogenes
• Growth-inhibiting tumour suppressor genes
• Genes that regulate programmed cell death (i.e., apoptosis)
• Genes involved in DNA repair

Question 6

Number of potentially-damaging DNA events per cell per day

Answer 6

~30,000 events. Almost all are repaired.

Question 7

Types of genetic abnormalities that increase chance of tumour development

Answer 7

Alterations to ability to repair DNA

Question 8

Difference between a mutation and a polymorphism

Answer 8

A mutation is any change in DNA sequence from normal.

A polymorphism is a DNA sequence variation common in the general population. No single allele is considered ‘normal’

Question 9

Effect of SNP in a promotor

Answer 9

Changes amount of protein produced

Question 10

Examples of DNA repair genes

Answer 10

BRCA1 and BRCA2

Question 11

Types of mutations in cancer
1
2
3
4

Answer 11

Errors in DNA replication not repaired
Point mutations
Copy number mutations
Chromosomal rearrangements

Question 12

Example of a gene that can amplify

Answer 12

N-MYC gene, associated with neuroblastomas.

Increases in copy number, greatly increases amount of gene expressed.

Question 13

Double minutes

Answer 13

Small fragments of extrachromosomal DNA, associated with cancers.

Question 14

Example of a gene translocation and fusion

Answer 14

BCR-ABL, leading to chronic myelogenous leukaemia.

ABL oncogene from chromosome 9, BCR locus on chromosome 22 swap.

Question 15

Size of a tumour that can be detected on an X ray

Answer 15

~10^8 cells

Question 16

How quickly can a tumour grow from 1g to 1kg?

Answer 16

~3 - 10 months, if unimpeded.

Question 17

Major cell proliferation pathways in cancer

Answer 17

Usually through a growth factor pathway (binding tyrosine kinase receptor).

PI3K pathway (Ras-dependent or -independent)

MAPK (always Ras-dependent)

Question 18

Manner in which RAS can be subverted in cancer

Answer 18

Made independent of upstream regulation.

Question 19

PI3K pathway
1
2
3
4

Answer 19

1) Tyrosine kinase receptor.
2) PI3K converts PIP2 to IP3. This is suppressed by P10 (tumour suppressor)
3) PIP3 phosphorylates, activates Akt, which activates CREB in the nucleus
4) Transcription of genes for cell survival growth, proliferation

Question 20

Difference in mutations required for cancer in oncogenes and tumour suppressor genes

Answer 20

Only need heterozygous mutation in oncogene.

Need homozygous mutations in tumour suppressors.

Question 21

Ways that tumour suppressor genes can be subverted

Answer 21

Mutation in gene, leading to non-functional protein
Deletion of gene
Hypermethylation of gene (epigenetic modification)

Question 22

miRNA

Answer 22

Small, non-translated RNAs.

Probably involved in regulating protein expression (both transcription and translation).

Question 23

First tumour suppressor gene identified

Answer 23

Retinoblastoma

Question 24

Prevalence of retinoblastoma

Answer 24

1/20,000 children

Question 25

Treatment and efficacy of treatment for retinoblastoma

Answer 25

Enucleation (removal of eye). Over 90% survival with early detection and treatment.

Question 26

LOH

Answer 26

Loss of heterozygosity.

Having a mutant allele of a tumour suppressor gene, and losing the one functional tumour suppressor allele.

Question 27

p53

Answer 27

Tumour suppressor gene. Lost in over 50% of cancers.

Question 28

Growth phases of cell cycle

Answer 28

G1 and G2

Question 29

Stage of cell cycle monitored by p53

Answer 29

S

Question 30

Stage of cell cycle monitored by retinoblastoma

Answer 30

G1

Question 31

Functions of Ras and MYC

Answer 31

Suppress p53 and Rb arrest of cell cycle

Question 32

Strategies for evasion of apoptosis 
1
2
3
4
5
6

Answer 32

(1) Reduced CD95 (Fas) level
(2) Inactivation of deathinduced
signaling complex by
FLICE protein
(3) Up-regulation of BCL2
(anti-apoptotic)
(4) Reduced levels of proapoptotic
BAX resulting from
loss of p53
(5) Loss of APAF-1
(6) Up-regulation of inhibitors
of apoptosis

Question 33

Ways to avoid intrinsic apoptotic pathway
1
2

Answer 33

(1) Reduced CD95 (Fas) level
(2) Inactivation of deathinduced
signaling complex by
FLICE protein

Question 34

Key anti-apoptotic molecule

Answer 34

BCL-2

Question 35

Most important pro-apoptotic molecule

Answer 35

Bax

Question 36

Ways to avoid extrinsic apoptotic pathway
1
2
3
4

Answer 36

(1) Up-regulation of BCL2
(anti-apoptotic)
(2) Reduced levels of proapoptotic
BAX resulting from
loss of p53
(3) Loss of APAF-1
(4) Up-regulation of inhibitors
of apoptosis

Question 37

Way in which cancer cells can have replicative immortality

Answer 37

Telomerase activity.

Question 38

Key stages in metastasis
1
2
3
4

Answer 38

1. Detachment of tumor cells from each other
2. Degradation of ECM
3. Attachment to novel ECM components
4. Migration of tumor cells

Question 39

Comparison between how normal and tumour cells grow in vitro

Answer 39

Normal cells form a contact-inhibited monolayer.

Tumour cells don’t have this inhibition, form lumps.

Question 40

How can metastatic cells escape from environment?

Answer 40

Either downregulate or degrade caderins, connexins that join them to other cells.

Question 41

Most important immune cell in signalling to accelerate, continue tumour growth

Answer 41

Macrophage

Question 42

Factors that drive tumour angiogenesis

Answer 42

VEGFs, VEGF-Rs (vascular endothelial growth factors)q

Question 43

Tumour-initiating cells

Answer 43

Stem cells which become cancerous.
Not very responsive to anti-cancer drugs (target quickly-dividing cells).
Slowly-dividing.