tumors and oncogenes

Question 1

oncogenes

Answer 1

genes that contribute to tumorigenesis by obtaining activating mutants, pushes cells towards its replicating stage for viruses to make copies

Question 2

sacroma

Answer 2

mesodermal tissue cancer

Question 3

carcinoma

Answer 3

endo/ectodermal tissue cancer

Question 4

nauroblastoma, glioblastoma, melanoma

Answer 4

neural cancer

Question 5

leukimia

Answer 5

blood cancer

Question 6

lymphoma, myeloma

Answer 6

lymph nodes, solid tumors

Question 7

LTR gene

Answer 7

carried by RNA tumor viruses, acts as promotor

Question 8

pol gene

Answer 8

by RNA viruses, reverse transcriptase, to transcribe RNA into DNA for integration in the hosts’
genome

Question 9

env gene

Answer 9

rna virus, is an envelop protein (host specific, e.g. specific for surface proteins of chick cells)

Question 10

gag

Answer 10

rna virus, structural rna binding protein

Question 11

onc

Answer 11

rna virus, viral oncogen transorms host making it oncogenic

Question 12

Ras

Answer 12

rat sarcoma, dominant mutation

Question 13

raf

Answer 13

rat fibrosacroma

Question 14

fos

Answer 14

feline osteosarcoma

Question 15

sis

Answer 15

simina (monkey) sarcoma,codes for PDGF B chain: results in increased levels of PDGF B and increased activation of receptor, c-SIS is human homolog and does not contain activating mutations, v‐SIS also does
not contain activating mutations, but its expression is increased in host cell via the LTR regions, v and c onc

Question 16

rna viruses

Answer 16

obtained oncogenic features, infect host with envelop proteins (gag, pol, env) and have them take up proto-oncogenes in their own viral genome

Question 17

3 types of oncogenes

Answer 17

‐ c‐onc with v‐onc homolog e.g. RAS, FOS, JUN
‐ c‐onc without v‐onc homolog e.g. kFGF, ErbB2
‐ v‐onc without c‐onc homolog  DNA tumor viruses

Question 18

DNA tumor viruses

Answer 18

bigger genome than RNA viruses, contain transforming genes
 Adenoviruses (E1A)
 SV40 virus (large T)
 Human Papillomavirus (E6; E7);
+ E1A, large T and E6/E7 are proteins that bind other proteins encoded by tumor
suppressor genes, proteins inactivate tumor supressor genes

Question 19

v onc

Answer 19

viral oncogens

Question 20

c onc

Answer 20

human or cellular oncogenes

Question 21

kKGF gene

Answer 21

activating mutations in promotor region of the gene, c onc

Question 22

EGFR mutations

Answer 22

1. no ligand domain -> ligand independent, activated by spontaneous dimer formation,
2. mutations in TK domain -> it keeps phosphorylating, keeps dividing

Question 23

RAS mutations

Answer 23

often mutated in human tumors, but also in other diseases/syndromes, such as
Costello syndrome, In tumor:
 mutations in intrinsic GTPase activity
 No return to GDP bound form
 RAS constitutively active

Question 24

RAF mutations

Answer 24

Mutations in V600E (Valine to glutamic acid) in melanoma
+ Valine has a neutral charge, while
glutamic acid has a negative charge
+ When proteins are phosphorylated,
they also obtain a negative charge
 The amino acid switch results in a
phosphorylation mimic.
 The protein is ‘activated’

Question 25

Vemurafenib

Answer 25

kinase inhibitor, interrupts RAF/MEK step, patient specific treatment, vemurafenib inhibits mutant RAF V600E specifically, however it activates other RAF mutants!

Question 26

FOA + JUN mutations

Answer 26

 truncation of mutation of regulating sequences (especially in RNA) making them constitutive active: FOS and JUN mRNAs are usually degraded quickly due to destabilizing elements in noncoding part of RNA, during oncogenesis these can be deleted  Gene duplication: multiple copies of the gene present in the genome

Question 27

tumor suppressor genes

Answer 27

 Genes that encode for proteins involved in suppressing oncogenesis, for example by inhibiting the cell cycle or inducing apoptosis  Three key examples RB, p53 and PTEN

Question 28

Retinoblastoma RB

Answer 28

retina/eye tumor, RB protein is a transcription repressor inhibiting gene activation, RB gene  inactivation 1 allele makes sufficient RB protein. both RB genes need mutations for mutation to show

Question 29

p53 gen/protein

Answer 29

tumor supressor gene, nuclear transcription factor, tumour cells have elevated expression of p53, makes other cells ongogenic, when mutated it becomes stable, complex of 4 copies of itself and needs only one of them mutated for the complex to inactivate, no genes will be transcribed, genes for growth inhibition, dominant negative mutation

Question 30

haplo insufficiency

Answer 30

1 allele is not enough for funcion, both allels are needed, VEGF mutations

Question 31

VEGF

Answer 31

needed to generate blood vessels, 2 alleles needed, but with one allele mutated phenotype visable -> aberrant blood vessel formation, dose from one allel = 90% and 100% is needed to be healthy