cancer genetics quiz three

protooncogenes

can be turned on or off to regulate the cell cycle

mutant forms of protooncogenes that are permanently switched on are called

oncogenes

oncoproteins change gene expression patterns directly or indirectly

to turn on cell proliferation

peyton rous

transmits sarcoma development from affected chickens and unaffected chickens using filtered tumor extract 

expresses mutant version of tyrosine kinase src to turn on cell cycle

RSV

multiple modes of protooncogene activation

point mutation, gene amp, chromosomal translocation, local DNA rearrangements, insertional mutagenesis 

protein coding-point mutation example

Ras oncoprotein blocks release of phosphorylation continually activating downstream of serine threonine. mutates GLY to VAL

chemotherapeutic agents that target members of the ras pathway

nib=kinase inhibitor, mab=monoclonal antibody

gene amplification example

human epidermal growth factor, HER2 amplicons can have up to 500 copies of the gene resulting in high levels of the receptor protein at the cell surface. onion skin replication, triggors oncoprotein pathways including RAS and SRC

chemotherapy for HER2

receptor dimerization and tyrosine kinase of her2 targeted 

chromosomal translocation example

Philadelphia chromosome, chromosomes 9+22 translocation resulting in the generation of a protein that fuses BCR with ABCL. 

drug that targets BCR and ABCL functions

imantin b/ Gleevac

insertional mutagenesis

upregulation of MYC expression, insertion of viral DNA places cell gene under regulation of viral gene expression. too much protein is made

gatekeeper tumor suppressor gene 

control cell growth directly

caretaker tumor suppressor gene

maintain stable genome

landscaper tumor suppressor genes

maintain normal tissue structure

landscaper example

SMAD4 
regulator of development and tissue homeostasis

caretaker example

p53 controls cell cycle and dna repair

gatekeeper example

APC mutations allow for more beta catenin