T&H7 Oncogenes and TSGs Flashcards
(88 cards)
1
Q
TSG or oncogene: p110
A
oncogene
2
Q
TSG or oncogene: EGFR
A
oncogene
3
Q
TSG or oncogene: ERBB2/HER2
A
oncogene
4
Q
TSG or oncogene: B-RAF
A
oncogene
5
Q
TSG or oncogene: K-RAS
A
oncogene
6
Q
TSG or oncogene: myc
A
oncogene
7
Q
TSG or oncogene: BCR-ABL
A
oncogene
8
Q
TSG or oncogene: IDH1/2
A
oncogene
9
Q
TSG or oncogene: JAK2
A
oncogene
10
Q
TSG or oncogene: KIT
A
oncogene
11
Q
TSG or oncogene: MET
A
oncogene
12
Q
TSG or oncogene: FLT-3
A
oncogene
13
Q
TSG or oncogene: p53
A
TSG
14
Q
TSG or oncogene: PTEN
A
TSG
15
Q
TSG or oncogene: p16
A
TSG
16
Q
TSG or oncogene: p14
A
TSG
17
Q
TSG or oncogene: BRCA1/2
A
TSG
18
Q
TSG or oncogene: LKB1
A
TSG
19
Q
TSG or oncogene: VHL
A
TSG
20
Q
TSG or oncogene: APC
A
TSG
21
Q
TSG or oncogene: FBXW7
A
TSG
22
Q
TSG or oncogene: Rb
A
TSG
23
Q
TSG or oncogene: NF1/2
A
TSG
24
Q
How long are miRNAs?
A
20-30 nucleotide RNA molecules
25
ABL kinase normally shuffles between nucleus and cytoplasm. Whenever it is mutated and forms fusion gene BCR-ABL, it is constitutively active and permanently found in the ______.
cytoplasm
26
How does imatinib target BCR-ABL?
binds in the vicinity of ATP-binding site and locks BCR-ABL in an inhibited conformation
27
What cancers are associated with BCR-ABL fusion oncoprotein?
most CML patients, ~30% adult ALL, ~10% pediatric ALL, occasionally AML
28
Myc promotes cell cycle progression by influencing a variety of targets, including downregulation of _______ and upregulation of _______, ____, ____, and _____.
- CDK inhibitors
- cyclin D1, CDK4, CDC25A, and E2F transcription factors
29
What is the paradoxical effect of myc?
upregulation can trigger apoptosis
30
Describe chromosomal translocation event in Burkitt LSA.
Chromosomal translocation between chromosome 8 (where myc resides) and chromosomes where IgH and light-chain genes reside, leading to overexpression of myc
31
myc targets _____ to cause tumor promoting inflammation in tumorigenesis.
IL-1beta
32
myc targets ____ to cause avoidance of immune destruction in tumorigenesis.
ICAM-1
33
myc targets _____ and _____ to deregulate cellular energetics in tumorigenesis.
GLUT-1 and LDHA
34
myc targets _______ and _____ to cause genomic instability in tumorigenesis.
MAD2 and BUBR1
35
myc targets _____ to activate metastasis in tumorigenesis.
ezrin
36
myc targets ____ to induce angiogenesis in tumorigenesis.
VEGF
37
myc targets ____ to enable replicative immortality in tumorigenesis.
TERT
38
What EGF family member cannot bind ligand, so it needs to be activated by dimerization with other family members?
ERBB2/HER2
39
An activating point mutation of EGFR leads to the receptor attaining an intermediate phosphorylation status, which activates ______ and ______ signaling at expense of other downstream pathways.
PI3K and MAPK
40
ERBB2/ERBB3 heterodimeric receptor complex is a potent signal transducer of which pathway and why?
- PI3K pathway
- ERBB3 receptor directly recruits PI3K rather than using intermediary adaptor proteins
41
ERBB2/HER gene is amplified in roughly ___% of all human breast cancers. What other cancers are associated with this amplification at a lower frequency?
25%
gastric and ovarian cancers
42
Amplification of ______ is generally an early event in breast cancer progression and is associated with poor prognosis in breast and gastric cancers.
ERBB2/HER2
43
Class IA PI3 kinases convert _____ to ____. This recruits PH domain-containing proteins, such as _____ and ______, to the plasma membrane for activation. _____ contributes to activation of _______, which then transmits signals downstream by phosphorylating a range of targets.
- PIP2 to PIP3
- AKT/PKB and PDK1
- PDK1
- AKT
44
_____ is a negative regulator of PI3K pathway by what mechanism?
- PTEN
- Acts as lipid phosphatase for PIP3
45
Activating mutations have been identified in the ______ gene, which encodes what subunit of PI3K?
- PIK3CA
- catalytic subunit p110
46
PIK3CA mutations result in what 3 outcomes?
- constitutive activation of PI3 kinase
- buildup of PIP3
- increased mobilization of downstream pathways
47
80% of all somatic PI3K mutations occur at 3 hotspot residues. Name them.
- E542K and E545K in helical domain
- H1047R in kinase domain
48
PI3 kinase pathway is generally overstimulated in cancers through ______, ________, and ____________.
- aberrant activation of receptors
- activating mutations of PI3 kinase catalytic subunit p110
- loss of PTEN
49
AKT can downregulate TSC1-TSC2 complex, which modulates what pathway?
RHEB GTPase - TORC1 signaling
50
______ is the most frequently mutated RAF family member. It it mutated in ____% of malignant melanomas in people.
B-RAF
40%
51
_____ substitution in the kinase activation loop accounts for _____ of all B-RAF mutations in people.
V600E
90%
52
_______ is an agent that targets BRAF mutation and shows marked improvement in patients with malignant melanoma.
vemurafenib
53
RAS and RAF lie downstream of ______ and upstream of _____ and ____.
- RTKs (primarily EGFR and PDGFR)
- MEK and MAPK
54
Ras can be activated by single point mutations in up to ___% of human cancers.
30%
55
What Ras gene is most commonly mutated?
K-RAS
56
What cancers are associated with K-RAS mutations?
pancreatic, lung, colon, endometrial, and ovarian
57
What cancers are associated with N-RAS mutations?
Neuronal cancer, melanoma, and myeloid malignancies
58
What cancers are associated with H-RAS mutations?
bladder cancer
59
The most common Ras mutations are gain of function substitutions in codons ___, ___, and ____. How is this mutations distinct?
- codons 12, 13, and 61
- Ras-GTPase enzymatic turnover is blocked by oncogenic mutations --> locks protein into activated GTP-bound signaling state --> upregulation of downstream effectors
60
What is the active Ras bound state?
GTP-bound Ras
61
What is the inactive Ras bound state?
GDP-bound Ras
62
____ is a novel oncogene which encodes isocitrate dehydrogenase, a Kreb cycle enzyme
IDH
63
IDH oncogene activation is seen in what type human cancers?
AML and glioblastoma multiforme
64
Most mutations in TP53 are _______ mutations.
missense
65
In response to DNA damage, _____ targets ___ which leads to phosphorylation of p53, thus blocking MDM2 and leading to its downstream effects.
ATM
CHK2
66
In response to oncogene activation, ________ inhibits MDM2 to allow p53 to do its job.
p14ARF
67
In response to cell stress, ___ targets ______ which phosphorylates p53, thus blocking MDM2 and leading to its downstream effects.
ATR
Casein kinase II
68
p53 targets ____ for DNA repair.
XPC
69
p53 targets ____ for cell cycle arrest or senescence.
p21
70
p53 targets ____ to inhibit angiogenesis.
thrombospondin
71
What pro-apoptotic proteins does p53 target?
- Bax
- PUMA
- p53AIP1
- NOXA
72
p53 targets what receptor, which leads to apoptosis.
FasR
73
p53 targets ____ which inhibits survival signaling.
IGFBP3
74
p53 downregulates what anti-apoptotic protein?
Bcl-2
75
BRCA1 is involved in the resection step of DNA DSB by ____ via interaction with _____.
HR
MRN complex
76
BRCA2 is a large protein that contains several regions. One region binds ____ and the other binds interacts with ____. What is its primary function?
- RAD51
- ssDNA
- Facilitate DNA repair by HR through recruitment of RAD51 to resected ssDNA
77
Tumors lacking BRCA1/2 are deficient in what repair pathway? These tumors can be targeted by _____, which is a good example of synthetic lethality.
- HR
- PARP inhibitors (involved in an alternative DNA repair pathway - BER)
78
_______ Rb binds E2F which prevents cell cycle progression.
hypophosphorylated
79
__________ phosphorylate Rb, which releases _____ allowing for cell cycle progression.
Cyclin/CDK complexes
E2F
80
Which RTK is activated in canine MCT and GISTs and how does it differ in these two tumors?
- c-kit
- c-kit mutations are common in GIST (60-70%) and minority in high-grade MCTs (20-30%)
- exon 9 and 11 for GIST (exon 11 highest for GIST)
- DOG1 only expressed in GIST
81
_____ phosphorylate GDP to GTP on RAS for activation while ___ de-phosphorylate to inactivate.
- GEFs (ie, SOS)
- GAPs
82
Name 2 transcription factors that when deregulated are associated with cancer in humans and dogs.
p53, myc
- myc: diffuse large B cell LSA and prostatic carcinoma, tvt in dogs
83
What is the critical step in the initiation of the apoptotic pathway? Hows does Bcl-2 influence this?
- critical step: creation of pores in mitochondria to release cytochrome C
- Bcl-2 is an anti-apoptotic protein that prevents apoptosis by sequestering caspases or by preventing release of mitochondrial apoptotic factors such as cytochrome C and AIF into the cytoplasm
84
Name the anti-apoptotic proteins
- Bcl-2
- Bcl-xl
- Bcl-w
- A1
- Mcl-1
- Boo
85
What are mechanisms of LOH?
1. Mitotic recombination
2. Gene conversion
3. Hemizygosity
4. Chromosomal translocations
5. Chromosomal non-disjunction
86
In canine lymphoma, abnormal p53 was associated with worse prognosis (MST _______ vs. ______).
MST 9 months
MST 2 months
87
What is the correlation between PTEN gene expression and biologic behavior in canine mammary tumors?
decreased levels of PTEN associated with malignancy and lymph node mets
88
