cancer genetics

Question 1

explain the clonal expansion model

Answer 1

there is one initiating mutation that gives a cell an advantage. after this more mutations happen and the cell will divide even faster. eventually you have a tumour. after this local invasion and even distal metastases can happen

Question 2

what is a mutation

Answer 2

a permanent alteration in a parental DNA sequence. the biological function does not need to be affected by this

Question 3

why does cancer still exist

Answer 3

• some mutations enhance cell proliferation and increase the mutation rate
• some mutations cause genomic instabillity
• mutation rate for some types are higher
• other mechanisms like epigenetics
• predisposing mutations in some people

Question 4

what are chromosome mutations

Answer 4

mutations that affect expression of many genes

Question 5

what are gene mutations

Answer 5

mutations that affect expression of a few genes

Question 6

with what does the beginning of an intron start and with what does it end

Answer 6

GT and ends with TC

Question 7

what effect do deletions or insertions in the following regions have

• introns
• promotor
• exon
• splice site

Answer 7

introns: usually no effect
promotor: may affect transcription efficiency
exon: may affect protein composition
splice site: may affect splicing (e.g. exon skipping)

Question 8

what is a nonsense mutation

Answer 8

a mutation in which a codon changes into a stopcodon

Question 9

what is a missense mutation

Answer 9

change in aminoacid

Question 10

what are oncogenes

Answer 10

genes which are mutated in a way that they can cause cancer

Question 11

what are charasteristics of oncogenes

Answer 11

• dominant, only one mutation is needed
• gain of function
• mostly missense mutations with mutational hotspot

Question 12

what are characteristisc of suppressor genes

Answer 12

• recessive, 2 hits needed
• loss of funciton
• truncating mutations over whole gene

Question 13

can you explain the RAS pathway and how it can be affected in case of a mutation

Answer 13

RAS is activated by GEF. it then starts downwards signalling which causes proliferation of the cell to happen. After this in a normal situation GAP will inactivate RAS. due to a mutation GAP will not be able to do this anymore and the cell will keep proliferating

Question 14

what is gene amplification and how can it cause gain of function. give two examples

Answer 14

amplification of a normal gene is that more of that gene is being made. this can be double minutes and HSR. examples are N-MYC gene (neuroblastomas) and the ERBB2 gene (breast, ovarian, gastic, colon and lung cancer).

Question 15

what does the (8;14)(q24;q32) translocation do

Answer 15

due to this translocation MYC will not be controlled by its own controller but by the IGH promotor. this causes excessive cell growth and is the cause of a lot of burkitt lymphomas

Question 16

what does the (9;22)(q34;q11) translocation do

Answer 16

this is the Philadelphia chromosome. you will get a fusion (p210) protein that can not be switched off anymore and will cause excessive cell growth. seen in a lot of chronic meyeloid leukamias

Question 17

what are tumor suppressor cells

Answer 17

cells with genes that surpress the development of cancer

Question 18

explain the second hit theory of knudsen

Answer 18

some people have bad genetics and will have already a predisposition for cancer, they will need only one hit to make cancer happen. other people dont have this, they develop sporadic cancer which needs 2 hits

Question 19

can you explain hypermethylation and hypomethylation (of the 5 position of the C)

Answer 19

hypermethylation –> chromatin closed –> no transcription –> loss of funciton
hypomethylation –> gain of function