molecular basis of cancer

Question 1

what does clonal mean?

Answer 1

genetic changes inherited when cells divide

Question 2

what is progression?

Answer 2

benign tumour to malignant, metastatic tumour

Question 3

3 environmental factors of getting cancer

Answer 3

diet, viruses, chemicals

Question 4

during natural selection(evolution of cells) what are the 4 different types of mutations?

Answer 4

1. initiating mutation
   2.second mutation
   3.third mutation
   4.fourth mutation

Question 5

what happens during initiating mutation ?

Answer 5

global expansion: evolution – cell that bypasses rules and regulation as single mutation gives survival advantages then the cells proliferate and grow more

Question 6

what happens during the second mutation?

Answer 6

then it accumulates and gives rise to more cells and the second clonal expansion begins.

Question 7

what happens during the third mutation?

Answer 7

proliferation continues and the third clonal expansion happens cells are uncontrollably, changing and growing

Question 8

what happens during the fourth mutation?

Answer 8

it has all these uncontrollable cells also due to proliferation

Question 9

in the fourth mutation, what is mild dysplasia ?

Answer 9

during single change is initiated cancer is not detectable but slow accumulation you can see mild dysplasia

Question 10

what are the 2 things mild dysplasia can turn into?

Answer 10

1.moderate dysplasia
2.severe dysplasia.

Question 11

what stage of cancer is situ carcinoma?

Answer 11

third stage of cancer

Question 12

what is invasive carcinoma?

Answer 12

cancer has started to spread in the body

Question 13

what are the 2 genes that lead to cancer?

Answer 13

1.oncogenes
2.protoncogenes

Question 14

what are oncogenes?

Answer 14

mutated form of normal genes that are involved in cell growth interaction and after doses

Question 15

what are protoncogenes?

Answer 15

normal cellular genes and include proteins which can regulate cell cycle, cell growth and cell differentiation and apoptosis

Question 16

how do protooncogenes get activate and convert to oncogene?

Answer 16

Converted by mutation, and if 1 allele is mutated this accelerates growth (it is dominant

Question 17

3 ways on how mutations happen and proton converts to oncogenes?

Answer 17

1.single point mutation: single nucleotide changes in DNA that is transcribed to RNA- leads to abnormal protein which is hyper active- could boost growth.
2.regulatory sequence in a mutation -multiple copies are transcribed and get overload of normal protein
3.gene amplification: gene itself is copied multiple times and transcribed to multiple RNAs and overload happens again

Question 18

during activation of photo-oncogenes, what is an example of single point mutation?

Answer 18

-H-ras(urinary tract cancer), K-ras (highly mutated in pancreatic cancer , N-ras (skin cancer EGFR

Question 19

during activation of photo-oncogenes, what are 2 examples of gene amplification?

Answer 19

Myc(transcription factor
-ERB2(growth factor receptors)

Question 20

what 2 mutations are involved during chromosomal translocation?

Answer 20

1.Myc
2.Bcr

Question 21

Map kinase pathway

Answer 21

works when growth factors bind to receptor, this pathway promotes growth and is a nutrition pathway

Question 22

Ras signalling pathway

Answer 22

ras is an enzyme(GTPASE) – hydrolysis to GTP to GDP, if the cycle gets stopped it was keeping the RAS active. Once it is active it hydrolyses to GDP then becoming active.

Question 23

what happens when mutation happens in ras signalling pathway?

Answer 23

the enzyme will lose the ability to hydrolase GTP to GDP so it will stay active meaning the pathways are switched for example AKT

Question 24

tumour suppressor genes

Answer 24

supress growth. Loss of tumour suppressor function leads to cancer.

Question 25

what happens during cancer when there is a gain of oncogenes

Answer 25

genes are switched on and when there is a loss of tumour suppressor genes which are switched off.

Question 26

how are there mutations in tumour suppressor genes?

Answer 26

They are not dominant they are recessive- they have recessive changes -one change in tumour will not lead to cancer there needs to be two events

Question 27

Knudson’s Two-hit hypothesis- loss of heterozygosity

Answer 27

needs to be 2 hits where the first will be single mutation and the second hit could be mutation itself or the lose part of the chromosome you have can have visitation but if there are both alleles that are affected changes will be seen -both events in gene and are affected meaning both adults are affected

Question 28

what do epigenetic changes show?

Answer 28

methylation in one of the genes and another pair of methylation so it needs 2 hits , one change in protooncogene to be activated to oncogene.

Question 29

what is main example of tumour?

Answer 29

suppressor gene p53 -mutated in 60% cancer

Question 30

what is suppressor gene p53 called ?

Answer 30

guardian of the genome

Question 31

what is suppressor gene p53 involved in?

Answer 31

DNA damage, telomere shortening, hypoxia, proliferation signalling, cell cycle arrest and apoptosis.

Question 32

what is function of suppressor gene p53

Answer 32

modulate DNA damage , it senses DNA damage and gives cell a signal whether to repair the change or go into apoptosis- protecting cell and genome from damage that occurs.

Question 33

how do mutations happen in p53 mutation?

Answer 33

when it is mutated there is nothing to tell the cell to that damage is there so cell cannot repair DNA and it cannot commit suicide which leads to combination of more damage.

Question 34

what happens when DNA replicates?

Answer 34

there is mutation in the DNA version there are no spell checkers

Question 35

How is Chronic Myelogenous Leukaemia (CML):blood cancer caused?

Answer 35

chromosomal reshuffle -9 fuses to chromosome 22 -leads to abnormal protein called BRC-ABL

Question 36

when chromosome 9 cuts off it fuses with 22 chromosome, what chromosome(9) does this lead to?

Answer 36

a long chromosome so chromosome 22 turns into small.Chromosome 22 has BCR(brain cluster region) -when chromosome fuses to this there will be abnormal protein which enzyme to kinase will be active

Question 37

Tyrosine kinase(enzyme

Answer 37

has advanced ETP which has an active binding site once its active it activates protein such as ras which leads to more growth

Question 38

what 2 drugs to block the tyrosine kinase?

Answer 38

1.imatinib 2.gleevec

Question 39

how can the 2 drugs block tyrosine kinase?

Answer 39

bind to enzyme which cannot phosphorylate the substrate so it won’t be active anymore -blocks ability of BCR-ABL kinase to phosphorylate the enzyme.