21 Carcinogenesis 2 Flashcards
What is the function of caretaker genes?
Maintain genetic stability by repairing damaged DNA and replication errors.
What are the two types of tumour suppressor genes?
Gatekeepers and caretakers.
What are the roles of gatekeeper genes?
Negatively regulate cell cycle + proliferation.
Positively regulate apoptosis + cell differentiation.
What are the most common mechanisms for the 2nd required for TSG inactivation? (4).
Chromosomal non-disjunction.
Gene conversion.
Mitotic recombination.
Promoter hypermethylation.
Which gene is involved in retinoblastoma?
What type of TSG is it?
RB1.
Gatekeeper.
Which gene is involved in Li-Fraumeni syndrome?
What type of TSG is it?
p53.
Gatekeeper/caretaker.
Which gene is involved in FAP?
What type of TSG is it?
APC.
Gatekeeper.
Which genes are involved in familial breast cancer?
What type of TSG is it?
BRCA1, BRCA2.
Caretaker.
Which gene is involved in HNPCC?
What type of TSG is it?
hMLH1, hMSH2.
Caretaker.
What are the functions of proto-oncogenes? (4).
Promote cell proliferation, survival, angiogenesis and regulation of apoptosis.
Are mutated porto-oncogenes dominant or recessive to the normal copy?
Dominant.
Are mutated tumour suppressor genes dominant or recessive to the normal copy?
Recessive.
What are the three mechanisms of oncogene activation?
Translocation to a transcriptionally active site.
Point mutation.
Amplification.
What is the minimum number of genetic alterations needed to transform a normal cell to a neoplastic cell?
3.
What are the genetic changes seen in the progression of colon carcinoma? (5).
Loss of APC. DNA hypermethylation. Activation of K-ras. Loss of 18qTSG. Loss of p53.
What are the hallmarks of cancer cells? (6).
Self sufficiency in growth signals. Insensitivity to anti-growth signals. Tissue invasion and metastasis. Limitless potential for replication. Sustained angiogenesis. Apoptosis evasion.
How do neoplastic cells become independent of growth signals? (4).
EGFR overexpression.
EGFR mutation.
Ras mutation.
B-Raf mutation.
How does a RAS mutation lead to independence from growth signals?
RAS in EGFR pathway.
Prevents dephosphorylation by GAP, and so becomes permanently active.
How do neoplastic cells become resistant to anti-growth signals?
Rb protein usually inhibits progression from G1 to S phase of cell cycle. -ve growth factors activate it.
Inactivation results in resistance to -ve growth factors.
How do tumour cells achieve immortality?
Over expression of telomerase enzyme maintains telomere length indefinitely.
What are telomeres?
Hexanucleotide repeat sequences. Shorten with each cell division, giving cells a finite replicative lifespan.
What is the most common gene mutated in human cancers?
TP53.
How do neoplastic cells become resistant to apoptosis?
TP53 mutation.
What is the function of TP53?
Induces cell cycle arrest to allow repair of DNA damage.
Induces apoptosis if too much damage.
How does angiogenesis occur in tumours?
Hypoxia stimulates HIF-1 transcription factor, inducing vascular endothelial growth factor (VEGF). VEGF actively recruits endothelial cells to construct new capillaries.
At what size do tumours start angiogenesis?
2mm in diameter.
How do tumours become invasive/metastatic? (At a genetic level).
Mutation/hypermethylation of E-cadherin prevents expression. Results in epithelial-mesenchymal transition (EMT). Mesenchymal cells are motile and secrete proteases, allowing them to break through membrane.
What is the CA-125 serum antigen used for? (3).
Identifying type of ovarian cancer.
Monitoring treatment success.
Detecting relapse.
Which AML translocations are associated with good prognoses?
t(8;21)
t(15;17)
inv(16)
Which AML translocations are associated with bad prognoses?
t(11q23)
complex karyotype
What does HER2 code for?
Change found in breast cancer?
Targeted drug?
+ve growth factor receptor.
Over expression.
Herceptin.
