GMS 6540 EXAM QUESTIONS AND ANSWERS WITH COMPLETE
SOLUTIONS VERIFIED LATEST UPDATE
Ras signaling
- GTPase
- promotes growth and proliferation
- mutated in 20-30% of all cancers
- point mutations are most common
G12V mutation
- blocks GAP binding
- locks RAS in active state, promoting proliferation
Q61K mutation
- raises activation energy of GTP hydrolysis
- blocking hydrolysis, keeping RAS active
Hallmarks of cancer
1) self-sufficiency in growth signals
2) insensitivity to anti-growth signals
3) unstable DNA
4) metastasis
5) evasion of apoptosis
6) abnormal cellular metabolism
7) angiogenesis
,8) inflammation
9) evasion of immune system
10) immortality
Anti-growth signals
- can be internal or external
- can be normal or induced
- must be overcame in normal cells to proliferate
p53
- damage sensor
- tumor suppressor gene
- halts cell cycle at G1 phase
- >50% of tumors contain mutation or deletion
R72P mutation
- block DNA binding
Rb
- binds E2F (transcription factor) blocking transcription
- when phosphorylated it releases E2F allowing transcription
Rb mutations
- mutated, present but unable to bind E2F
- downregulated, allows for further transcription
- CDK overactivity - allows for Rb to be phosphorylated
Unstable DNA
,- genetic instability
- chromosomal instability
- enabling hallmark
- can cause drug resistance
Chromosomal instability
- gain or loss of whole chromosomes
- can get double or quadruple genomes
- gain of pro-growth/invasive genes
- loss of growth inhibitory genes
Endoreduplication
- replication without nuclear division
- failed cytokinesis
Multipolar spindles
- monopolar spindle
- lagging chromosomes
Metastasis
- cancer cells move into blood and relocate
- cause 90% of deaths from solid tumors
- 30-40% of newly diagnosed patients have detectable metastases
- 20-30% of remaining patients are clinically free of metastases harbor hidden
metastases
Apoptosis
, - programmed cell death (suicide)
- cell volume loss
- membrane blebbing
- formation of
- apoptotic bodies
- DNA fragmentation & condensation
- collapse of cytoskeleton
- immune cell engulfment
- non-inflammatory
Intrinsic apoptotic stimuli
- DNA damage - senese by P53
- loss of survival hormones
- cell detachment from designated area (anoikis)
- radiation
- increased levels of oxidants
- chemo
Extrinsic apoptotic stimuli
- death receptor death ligand binding
- expression of abnormal cell surface antigens
Strategies to escape apoptosis
- increased expression of anti-apoptotic proteins
- downregulation of pro-apoptotic proteins
- elevated expression of death ligands on tumor
SOLUTIONS VERIFIED LATEST UPDATE
Ras signaling
- GTPase
- promotes growth and proliferation
- mutated in 20-30% of all cancers
- point mutations are most common
G12V mutation
- blocks GAP binding
- locks RAS in active state, promoting proliferation
Q61K mutation
- raises activation energy of GTP hydrolysis
- blocking hydrolysis, keeping RAS active
Hallmarks of cancer
1) self-sufficiency in growth signals
2) insensitivity to anti-growth signals
3) unstable DNA
4) metastasis
5) evasion of apoptosis
6) abnormal cellular metabolism
7) angiogenesis
,8) inflammation
9) evasion of immune system
10) immortality
Anti-growth signals
- can be internal or external
- can be normal or induced
- must be overcame in normal cells to proliferate
p53
- damage sensor
- tumor suppressor gene
- halts cell cycle at G1 phase
- >50% of tumors contain mutation or deletion
R72P mutation
- block DNA binding
Rb
- binds E2F (transcription factor) blocking transcription
- when phosphorylated it releases E2F allowing transcription
Rb mutations
- mutated, present but unable to bind E2F
- downregulated, allows for further transcription
- CDK overactivity - allows for Rb to be phosphorylated
Unstable DNA
,- genetic instability
- chromosomal instability
- enabling hallmark
- can cause drug resistance
Chromosomal instability
- gain or loss of whole chromosomes
- can get double or quadruple genomes
- gain of pro-growth/invasive genes
- loss of growth inhibitory genes
Endoreduplication
- replication without nuclear division
- failed cytokinesis
Multipolar spindles
- monopolar spindle
- lagging chromosomes
Metastasis
- cancer cells move into blood and relocate
- cause 90% of deaths from solid tumors
- 30-40% of newly diagnosed patients have detectable metastases
- 20-30% of remaining patients are clinically free of metastases harbor hidden
metastases
Apoptosis
, - programmed cell death (suicide)
- cell volume loss
- membrane blebbing
- formation of
- apoptotic bodies
- DNA fragmentation & condensation
- collapse of cytoskeleton
- immune cell engulfment
- non-inflammatory
Intrinsic apoptotic stimuli
- DNA damage - senese by P53
- loss of survival hormones
- cell detachment from designated area (anoikis)
- radiation
- increased levels of oxidants
- chemo
Extrinsic apoptotic stimuli
- death receptor death ligand binding
- expression of abnormal cell surface antigens
Strategies to escape apoptosis
- increased expression of anti-apoptotic proteins
- downregulation of pro-apoptotic proteins
- elevated expression of death ligands on tumor
