33_Tumour suppressors, proto-oncogenes & oncogenes Flashcards
Tumour suppressors are characterized by (LoF/GoF) mutations.
LoF
What tumour suppressor is used as a prognostic factor to assess chance of metastasis? Why?
E-cadherin
provides strength to tissue and protection against cancer
What is the chance of developing retinoblastoma if a patient has inherited one mutant allele of the RB gene?
90%
What are BRCA1 and BRCA2?
DNA repair proteins that are mutated in many cases of hereditary breast cancers
What does MDM2 do? If mutated, what effect does it have?
It inhibits p53.
mutated = oncogene
What is the issue with p53 mutants and their response to chemotherapy agents?
Many chemotherapy agents use DNA damage to affect cancer cells. If p53 is lost, cells can continue to proliferate despite DNA damage.
What is the difference between proto-oncogenes and oncogenes?
Proto-oncogenes encode proteins that accelerate cell proliferation. Oncogenes are abnormally-expressed/mutated forms of proto-oncogenes that promote loss of growth contro.
What are some examples of proto-oncogenes?
FAK, Src, Ras, Bcl-2, Cyclin D, Raf-1, ß-catenin
Oncogenes are characterized by (LoF/GoF) mutations.
GoF
How does ß-catenin function as an oncogene?
In the adherens junction, involvement of ß-catenin in a signalling pathway results in destabilization of the junction
=> migration
Which proto-oncogenes are located at focal adhesions?
FAK, Src, Ras, Raf
What are some proto-oncogenes in the MAPK cascade?
Fos & Jun, Cyclin D, Ras, Raf
In what ways can proto-oncogenes become oncogenic?
1) mutations in coding region leading to changed structure/function
2) mutation of regulatory sequence leading to increased expression
3) chromosomal rearrangements leading to altered structure/function
Which mechanism of conversion of proto-oncogenes to oncogenes can result in the formation of chimera?
chromosomal rearrangement (chimera or fusion gene; common in some leukemias)
