Cancer

Question 1

Kandoth 2013

Answer 1

analysed gemome sequences of 3,281 tumors of 12 common cancer types
127 significantly mutated genes
most tumors had 2-6 of these

Question 2

errors in DNA mismatch repair

Answer 2

HNPCC

Question 3

errors in NER

Answer 3

Xeroderma pigmentosum

Question 4

errors in homologous recombination repair

Answer 4

hereditary breast and ovarian cancer

Question 5

hallmarks of cancer (6)

Answer 5

1. resisting cell death
2. sustaining proliferative signalling
3. evading growth suppression
4. activation invasion and metastasis
5. enabling replicative immortality
6. inducing angiogenesis

Question 6

Dominant mutations (3)

Answer 6

EGFR, HER2, RAS

Question 7

Loss of function mutations (3)

Answer 7

RB-1, VHL, TP53

Question 8

Knudson 1971

Answer 8

retinoblastoma - two hit hypothesis

Question 9

defective p53 in cancer (3)

Answer 9

MDM2 overexpression, loss of ATM function, loss of ARF

Question 10

Role of p53

Answer 10

activates transcription of MDM2 - encodes a ubiquitin ligase targeting p53 for degradation
p53 is stabilised by bocking the MDM2-p53 interaction
p53 is activated in response to diverse stresses - blocks CDK activity - promotes cell arrest to allow DNA repair/apoptosis

Question 11

Classes of Cytotoxic Cancer Drugs

Answer 11

1. antimetabolites
2. alkylating agents
3. topoisomerase inhibitors
4. anti-mitotic agents

Question 12

Methotrexate

Answer 12

antimetabolite
competitive inhibitor of DHFR
inhibits biosynthesis of purines and inhibits replication and DNA replication

Question 13

Doxorubicin

Answer 13

intercalating agent

inhibits DNA topoisomerase II

Question 14

Vincristine

Answer 14

Anti-microtubule agent
inhibits tubulin polymerisation
prevents assembly of mitotic spindle