Cancer I and II

Question 1

6 hallmarks of cancer

Answer 1

evading apoptosis
self-sufficiency in growth signals
insensitivity to anti-growth signals
sustained angiogenesis
limitless reproductive potential
tissue invasion and metastasis

Question 2

example of how limitless replicative potential can emerge

Answer 2

acquisition of telomerase function, blocks to differentiation

Question 3

example of a cancer which can emerge via a chromosomal translocation mutation

Answer 3

CML

Question 4

examples of mutations which can cause cancer

Answer 4

chromosome instability, amplification or deletion of regions, base pair mutations

Question 5

Kataegis

Answer 5

clustered nucleotide substitutions, a type of localised mutagenesis which can exist in cancer cells

Question 6

Xeroderma pigmentosum

Answer 6

early onset skin cancer- hypersensitivity to UV light caused by mutations in nucleotide excision repair which allow error-free copying of thymidine dimers that can potentially cause cancer

Question 7

lynch syndrome

Answer 7

condition leading to a high chance of developing early-onset colorectal cancer, issue with Mut proteins used in repair- these proteins recognise the distorted strand

Question 8

BRCA gene

Answer 8

involved in the repair of DSBs using homologous recombination, which is more accurate than the alternative (NHEJ)- BRCA genes stimulate end resection and strand invasion

Question 9

possible mechanism of oncogene induced replication stress

Answer 9

lack of dNTPs, histones, replication proteins etc leading to more fork stalling, DNA breaks etc- possibly leading to concentrations of mutations

Question 10

most frequently mutated gene

Answer 10

p53

Question 11

name of the technique used to determine where a cancer may have originated

Answer 11

mutational signature analysis

Question 12

3 familial cancer syndromes and the mutations which cause them

Answer 12

Li-Fraumeni syndrome- p53
Retinoblastoma- Rb
Hereditary Breast and Ovarian Cancer (HBOC) syndrome- BRCA1/2

Question 13

p53 function

Answer 13

transcription factor for genes like cyclin-CDK2

Question 14

what normally keeps p53 levels low

Answer 14

interactions with ubiquitin ligase

Question 15

Rb function

Answer 15

transcriptional repression- its mutation can therefore lead to overexpression of DNA replication genes

Question 16

example of an oncogenic virus

Answer 16

RSV- leads to src being inserted into tge genome, potentially leading to cancer by displacement or mutation of important bits of the genome- can also spread cancer through packaging mutated DNA

Question 17

Src

Answer 17

encodes a tyrosine kinase, involved in growth factor signalling

Question 18

example of rational therapy in CML

Answer 18

inhibition of Bcr-Abl kinase that causes the expansion of cells with imatinib, preventing downstream regulation by these ongogenic kinases

Question 19

rational therapy which inhibits growth factor receptors

Answer 19

herceptin- monoclonal antibody binding Her2, which is upregulated in breast cancer

Question 20

example of rational therapy for BRCA mutant cells

Answer 20

PARP-targeted drugs, trapping these PARPs seems to lead to DSBs accumulating and the cells dying- e.g. olaparib