tumors and oncogenes Flashcards
oncogenes
genes that contribute to tumorigenesis by obtaining activating mutants, pushes cells towards its replicating stage for viruses to make copies
sacroma
mesodermal tissue cancer
carcinoma
endo/ectodermal tissue cancer
nauroblastoma, glioblastoma, melanoma
neural cancer
leukimia
blood cancer
lymphoma, myeloma
lymph nodes, solid tumors
LTR gene
carried by RNA tumor viruses, acts as promotor
pol gene
by RNA viruses, reverse transcriptase, to transcribe RNA into DNA for integration in the hosts’
genome
env gene
rna virus, is an envelop protein (host specific, e.g. specific for surface proteins of chick cells)
gag
rna virus, structural rna binding protein
onc
rna virus, viral oncogen transorms host making it oncogenic
Ras
rat sarcoma, dominant mutation
raf
rat fibrosacroma
fos
feline osteosarcoma
sis
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
rna viruses
obtained oncogenic features, infect host with envelop proteins (gag, pol, env) and have them take up proto-oncogenes in their own viral genome
3 types of oncogenes
‐ 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
DNA tumor viruses
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
v onc
viral oncogens
c onc
human or cellular oncogenes
kKGF gene
activating mutations in promotor region of the gene, c onc
EGFR mutations
- no ligand domain -> ligand independent, activated by spontaneous dimer formation,
- mutations in TK domain -> it keeps phosphorylating, keeps dividing
RAS mutations
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
RAF mutations
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’
Vemurafenib
kinase inhibitor, interrupts RAF/MEK step, patient specific treatment, vemurafenib inhibits mutant RAF V600E specifically, however it activates other
RAF mutants!
FOA + JUN mutations
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
tumor suppressor genes
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
Retinoblastoma RB
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
p53 gen/protein
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
haplo insufficiency
1 allele is not enough for funcion, both allels are needed, VEGF mutations
VEGF
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