cancer hallmarks 1

Question 1

what is tumourigenesis

Answer 1

process which normal cells transform into cancerous cells, leading to the formation of tumours

Question 2

describe steps of tumourigenesis

Answer 2

1. initiation-single genetic event
2. promotion-clonal expansion
3. progression-increased genetic/chromosomal instability, accumulation of mutations, increasingly aggressive phenotype
4. metastasis

Question 3

what is metastasis

Answer 3

development of secondary malignant growths at a distance from a primary site of cancer

Question 4

what is proliferation and what is it controlled by

Answer 4

cell division, by proto oncogenes

Question 5

what is apoptosis and what is it controlled by

Answer 5

cell death, by tumour suppressor genes

Question 6

in short what causes cancer

Answer 6

increased proliferation, no apoptosis, homeostasis pertubed

Question 7

how do oncogenes disrupt signalling and examples

Answer 7

-some oncogenes force cells to overproduce growth factors
eg. sarcomas, gliomas- release excessive platelet derived growth factors

-some product aberrant or elevated receptors, releases proliferative signals even in absence of growth factors
eg. Her2 (Erb-B2)

-some perturb signalling cascade in cytoplasm
eg. mutant Ras

-some alter activity of nuclear transcription factors
eg. c-myc

Question 8

what is the first hallmark of cancer

Answer 8

self sufficiency in growth signals

Question 9

proto oncogenes vs oncogenes

Answer 9

proto oncogenes=normal genes that regulate cell growth and division

oncogenes=mutated/overexpressed version of protooncogenes that can lead to uncontrolled cell growth and potentially cancer

Question 10

what are translocation mutations

Answer 10

type of chromosomal rearrangement where a segment of one chromosome breaks off and reattaches to a different chromosome or even a different part of the same chromosome

Question 11

what is the pathogenesis (cause of development) of CML and what is CML

Answer 11

CML=chronic myeloid leukaemia
pathogenesis=translocation mutation

Question 12

what mimics growth factor activation

Answer 12

Bcr-Abl signalling

Question 13

what happens if a point mutation occurs

Answer 13

-a single base is altered
-codon altered
-different amino acid
-protein function changes

Question 14

what is the most common carcinogenic oncogene in human cancer

Answer 14

mutant KRAS

Question 15

what is the function of the RAS family

Answer 15

turns cell signalling on or off

Question 16

what happens when KRAS is mutated

Answer 16

cell signalling is permanently on, leads to uncontrolled cell proliferation

Question 17

describe how KRAS gets mutated

Answer 17

point mutations in codons 12,13 or 61, leading to constitutive activation of growth stimulatory signals and tumour formation

codon 61=CAA to AAA=glutamine to lysine

Question 18

what is the 2nd hallmarks of cancer

Answer 18

insensitivity to growth inhibitory signals

-cancer cells evade/ignore breaking signals issued by normal cells

Question 19

what codon change causes insensitivity to inhibitory signals/inactive function

Answer 19

P53 protein codon 273=G to A=arginine to histidine=inactive function

Question 20

what is P53 protein’s function

Answer 20

(guardian of genome) stops cell cycle in response to DNA damage, promotes DNA repair, induces apoptosis

Question 21

what is Li-Fraumeni syndrome and what cancers are associated with it

Answer 21

inherited cancer predispositions caused by germline mutation in P53/ caused by mutations in the TP53 gene (TP53 codes for P53)

-breast, brain tumours, leukemia, osteosarcoma, soft tissue sarcoma

Question 22

what protein is the guardian of the genome

Answer 22

P53

Question 23

what happens if P53 is mutated

Answer 23

DNA damage is unchecked, mutations build up

Question 24

describe the cell cycle

Answer 24

G1=production of RNA and enzymes needed for DNA synthesis

S=DNA synthesis

G2=preparation for mitosis, specialised proteins synthesised

M=prophase, metaphase, anaphase, telophase, division to form 2 daughter cells

Question 25

what is Rb protein and its function

Answer 25

retinoblastoma protein, tumour suppressor (prevents cells from dividing when not supposed to), antiproliferative signals

Question 26

how does Rb act as a tumour suppressor

Answer 26

Rb turns to hypo phosphorylated Rb and blocks proliferation by binding and inhibiting E2F transcription factors so cells stay in G1

Question 27

what are E2F transcription factors essential for

Answer 27

G1 to S progression

Question 28

what is the active and inactive form of Rb

Answer 28

active=hypo phosphorylated inactive=hyper phosphorylated, doesnt bind to E2F and allows cells to transit to S phase

Question 29

what does active Rb do

Answer 29

bind to E2F and stops G1 to S progression

Question 30

what is the 3rd hallmark of cancer

Answer 30

evasion of apoptosis

Question 31

what triggers apoptosis

Answer 31

P53

Question 32

what happens when apoptosis is inactivated

Answer 32

reduces elimination of damaged cells, cells harbour dangerous mutations, cancer cells synthesises excessive amounts of survival proteins

Question 33

DNA damage leads to genetic mutations, what causes damage to DNA

Answer 33

cellular metabolism, UV light, ionising radiation, chemical exposure, replication errors

Question 34

what are driver genes

Answer 34

genes who's mutations pushes cell towards cancer, oncogenes/tumour suppressor genes if mutated/lost function

Question 35

what are gatekeeper genes

Answer 35

tumour suppressors that directly control cell division checkpoints, regulates cell growth and removes damaged cells from replication cycle