1. introduction and nomenclature

Question 1

when work is done on model organisms, what is needed to be done with the data?

Answer 1

it needs to be extrapolated back and made relevant to humans

Question 2

what is cancer?

Answer 2

a group of diseases generally characterised by genomic instability and uncontrolled cell division and leading to invasion of surrounding tissue and eventually dispersal to different sites

Question 3

what does this general description of cancer not take into account?

Answer 3

fluid tissues i.e. blood cancer

Question 4

there are over 200 different clinical classifications of cancer, what does this equate to?

Answer 4

200 cells types of the body

Question 5

what are the four biggest cancer killers?

Answer 5

breast cancer
lung cancer
large bowel cancer
prostate cancer

Question 6

what percentage of cancer mortalities are due to lung cancer? and what is this almost entirely due to?

Answer 6

14%

smoking

Question 7

why is colon cancer so prevalent?

Answer 7

this is a highly proliferative tissue

Question 8

give a reason that cancer is so hard to treat

Answer 8

no two cancers are the same

Question 9

name the type of cancer that arises in the epithelial layer and what percentage of cancers arise here?

Answer 9

carcinoma

90%

Question 10

name they type of cancer that arises in the connective tissue and bone (non-epithelial tissue)

Answer 10

sarcoma

Question 11

name the type of cancer that arises in plasma cells

Answer 11

myeloma

Question 12

what is leukaemia and what does it affect?

Answer 12

blood cancer that arises in the bone marrow and can affect circulation

Question 13

what is a mixed tumour? and how is it diagnosed?

Answer 13

this is a tumour that is derived from multiple tissues, it is diagnosed by looking at histological samples

Question 14

what is a risk factor for cancer? and why is this?

Answer 14

age, genome accumulates mutations throughout life

Question 15

what is amazing about how many cells there in our body and what does this show?

Answer 15

all 10^4 cells in our body arose from a single cell, given the number of cell divisions and DNA copied its amazing we don’t get more cancer. this shows that we have good replication and repair machinery in place.

Question 16

give four factors that can contribute to mutations arising in our genome?

Answer 16

• exposure to radiation or carcinogens
• hereditary disposition
• DNA damage by ROS
• viral infection

Question 17

name two types of genes that if mutated give rise to genomic instability?

Answer 17

tumour suppressers and oncogenes

Question 18

what is a tumour suppresser and what has to occur for it to promote cancer formation?

Answer 18

a tumour suppresser is a gene that prevents cancer from occurring, when mutated it loses its function

Question 19

what is an oncogene and what has to occur for it to promote cancer formation?

Answer 19

an oncogene is a gene that when it functions abnormally, promotes tumour growth, when a proto-oncogene is mutated it has a gain of function and becomes oncogenic

Question 20

what type of gene mutation makes a more easy therapeutic target?

Answer 20

oncogene, as you cannot target something that is not there i.e. a lost tumour suppresser

Question 21

what did Peyton Rous see in 1911? and what was he the first person to recognise?

Answer 21

he saw that sarcomas were transmissible between chickens, he used cell free tumour extract to infect chickens and saw them develop tumours, showing an inheritable basis for this type of tumour
he recognised the presence of oncogenes

Question 22

what retrovirus was Peyton Rous infected his chickens with?

Answer 22

Rous Sarcoma Virus

Question 23

describe the genome of a retrovirus

Answer 23

relatively small RNA genome

Question 24

what is at either end of the retroviruses genome?

Answer 24

at either end of the genome there are long terminal repeats (LTRs) so that the virus can insert itself into the host genome.

Question 25

what are the genes encoded for by a retrovirus genome?

Answer 25

ENV - encodes envelope genes
POL - encodes reverse transcriptase (makes DNA from RNA for insertion into host genome)
GAG - encodes capsid proteins to protect genome from environment

Question 26

what is the additional gene found in RSC that will lead to cancer? and what type of gene is this?

Answer 26

vSRC

it is a transforming gene because it is able to turn normal cells into cancer cells

Question 27

what is the difference in sequence between vSRC and cSRC? and what does this difference mean?

Answer 27

cellular SRC has an extension at the C terminus and a substitution mutation of glutamine to phenylalanine
this difference accounts for the fact that vSRC is transforming and cSRC is not

Question 28

name the domain that binds phosphotyrosines

Answer 28

SH2

Question 29

name the domain that binds proline rich sequences

Answer 29

SH3

Question 30

from N to C terminus list the domains and important features of SRC

Answer 30

SH3, SH2, kinase domain, Tyrosine 527

Question 31

what type of kinase domain does SRC have and what does it do?

Answer 31

tyrosine kinase that transfers gamma phosphate of ATP onto tyrosine

Question 32

describe the inactive form of SRC?

Answer 32

• SH2 binds phosphotyrosine 527
• SH3 bind proline rich domain between SH2 and SH1.
• this squeezes catalytic domain shut and so stops substrate from binding

Question 33

what form is cSRC normally found it?

Answer 33

inactive, but can be switched on if needed

Question 34

why cant vRSC be inactivated?

Answer 34

it lacks the C terminal Tyrosine 527 and so is constitutively active

Question 35

name 4 retroviral oncogenes and what type of protein are they?

Answer 35

Src - tyrosine kinase
Ras - GTPase (constitutively active)
Fos - transcription factor (lacks P site for nuclear exclusion)
Sis - platelet derived growth factor (growth factor constantly expressed)

Question 36

what are the cellular version of these viral oncogenes?

Answer 36

proto-oncogenes

Question 37

what type of mutations may make a proto-oncogene oncogenic? (4)

Answer 37

• point mutation
• truncation
• gene amplification
• chromosomal translocation

Question 38

what is the most commonly mutated gene in human cancer? and define the most common mutation

Answer 38

Ras

conserved glycine mutated to valine

Question 39

what are many cancers initiated by? these are most common in tumours, how does this have an effect on therapies?

Answer 39

loss of tumour suppresser

you cannot drug something that is not there

Question 40

describe the Knudson’s two hit hypothesis

Answer 40

in order to inactivate a tumour suppresser, two genetic mutations need to occur. mutations can be sporadic or familial. in the case of sporadic, two somatic mutations need to occur. in the case of familial, only one somatic mutations needs to occur as the first is inherited.

Question 41

who was knudson and what did he do?

Answer 41

he was a surgeon that look at the pedigree of retinal cancer and formed a hypothesis on tumour suppressers based on classical genetics

Question 42

how many mutation need to occur to activate an oncogene and how it this different for tumour suppresser?

Answer 42

one

two mutations need to occur to knock out TS function

Question 43

how do sporadic and familial tumour suppresser losses differ in terms of when and what type of tumour formations occur?

Answer 43

• sporadic tumour are late onset and single tumour

- familial tumours are early onset and multiple tumours

Question 44

once the first hit is occurred and chromosomes are heterozygous, what needs to happen for a loss of TS? and when this happens at a certain location what it this an indictor of?

Answer 44

loss of heterozygosity at a certain location is an indicator of a TS

Question 45

why is only one mutation in oncogenes enough to drive cancer?

Answer 45

even through you have one WT copy of the gene still, you have one constitutively active copy that will drive cancer

Question 46

whats the difference between the difference types of mutations that can lead to loss of TS and gain of oncogene?

Answer 46

many different types of mutations can occur in order to lose an oncogene, but define mutations have to occur to generate an oncogene