Cancer Flashcards
Most mutations are ______ and occur _______. They require _______
Somatic
post-fertilization
Multiple mutations
Oncogenes
Promote cell growth and division
Try more suppressor classes (2)
Caretaker
Gatekeeper
Caretaker genes
Prevent or repair damage to DNA
Lose these genes = promote genetic change
Gatekeeper
Restrain cell division or induce apoptosis
Lose these genes = uncontrolled proliferation
Loss of heterogeneity
Inheriting one bad copy can cause the good copy to go “bad”
Retinoblastoma caused by
Loss of function of Rb
Rb inhibits ____ which inhibits _____
E2F
G1/S transition
Rb prevents cell division
Sporadic Retinoblastoma
Late and rarely
1 tumor in 1 eye in 1 person in a family
Familial Retinoblastoma
Early and often
Bilateral tumors
Multiple members affected
P53 stimulates txn of: (2)
CDK inhibitors
Pro-apoptotic factors
P53 is destabilized by _____
Mdm2
P53 is stabilized by: (2)
DNA damage
P14ARF
P14ARF is a ______ made from _______ which encodes _______
Protein
Growth factors
CDK inhibitors
Proto-oncogene
Gene that can become an oncogene if mutated or expression increases
Oncogenes
Can cause cancer when activated or expressed
MTOR pathway
Promotes cell growth and protein synthesis
Commonly mutated in tumors
Viral oncogenes
Normally promote cell division
Derived from genome of host cell
Overproduction of c-myc by: (2)
Gene amplification (inc. number of gene copies) Chromosomal translocations to inc. txn of c-myc
Homogenously-staining region
Amplification of c-myc
Copies are duplicated in same region inside chromosome
Double minute chromosome
Amplification of c-myc
Duplicated copies in same region outside of chromosome
Detect overproduction of c-myc by:
Metaphase FISH
Burkett Lymphoma
B lymphocyte cancer
C-myc controlled by antibody gene enhancer which increases lymphomas
C-abl
Changes genetically to self-activate
Does NOT need regulatory stimuli
NF1 proteins is a
Ras-GAP
Mutation leads to Neurofibromatosis
Ras family (2)
Receptor signaling
Cell division
Ran family
Nucleus/ cytoplasm traffic
Rac family
Actin cytoskeleton
Rab family
Traffic of membrane vesicles
Oncogenic mutations in Ras
AA substitutions of gly12 and gln61
Reduce GTPase activity or ras
Mostly in active state
C-ras mutation prevents
Inactivation
Clinical features of CML (3 main ones)
Splenomegaly
Elevated WBC count
Early satiety
CML is a ________ disorder so it _________ but does NOT ______
Myeloproliferative
Increases proliferation
Lose ability to differentiate
CML cause is a
Balanced translocation of chr22 (bcr) and chr9 (abl)
Philadelphia chromosome
Chimeric protein from the translocation
C-abl regulates ______ and is normally located in the _____
DNA damage repair response and promotes growth
Nucleus
Bcr-abl protein is
Trapped in the cytoplasm thereby altering the DNA damage repair response
Constitutively active
Bc-abl promotes CML development by: (3)
Uncontrolled proliferation
Escapes apoptosis
Alter interaction with ECM
C-abl gains ______from bcr to facilitate _____
A domain
Dimerization
C-abl creates a ______ so it can _____ to ________
Gain of function
Auto-phosphorylate
Become active
C-abl is able to auto-phosphorylate because
It’s a tyrosine kinase
