Chapter 7 Flashcards
1
Q
desmoplasia
A
abundant collagenous stroma
benign
2
Q
scirrhous
A
benign stony hard tumors (breast)
3
Q
sarcomas
A
arise from mesenchyme and have little CT
4
Q
carcinomas
A
arise from epithelium
5
Q
squamous cell carcinoma
A
tumor cells resemble stratified squamous epithelium
6
Q
mixed tumors
A
divergent differentiation of single neoplastic clone along 2 lineages, but only one germ layer involved
7
Q
pleomorphic adenoma
A
arise from mixed tumors
most common in parotid gland
8
Q
malignant tumors that sound benign
A
lymphoma
melanoma
mesothelioma
seminoma
9
Q
hematomas
A
disorganized, benign cells
10
Q
choristoma
A
congenital anomaly
heterotopic rest of cells
11
Q
anaplasia
A
lack of differentiation
12
Q
major components of anaplasia
A
pleomorphism
abnormal nuclear morphology
mitoses
loss of polarity
13
Q
minor components of anaplasia
A
tumor giant cells (don’t confuse w/langhans cells)
central necrosis
14
Q
autosomal dominant cancers
A
childhood retinoblastoma familial adenomatous polyposis Li-Fraumen syndrome multiple endocrein neoplaia 1 and 2 HNPCC
15
Q
childhood retinoblastoma
A
RB tumor supressor gene
16
Q
familial adenomatous polyposis
A
APC tumor supressor gene
17
Q
multiple endocrine neoplasia type 1 and 2
A
MENI TF
RET tyrosine kinase genes
18
Q
HNPCC
A
hereditary non-polyposis colon cancer
inactivation of DNA mismatch repair gene
19
Q
defective DNA syndrome
A
usually autosomal recessive
xeroderma pigmentosum, ataxia-telangiectasia, bloom syndrome
HPNCC most common
20
Q
glioblastomas often secrete what GF
A
PDGF
21
Q
sarcomas often secrete what GF
A
TGF alpha
22
Q
RET gene
A
MEN2a and 2b and medullary thyroid cancer
23
Q
RAS
A
point mutations in this family is single most common abnormality of proto-oncogenes in humans
24
Q
KRAS
A
carcinomas of colon and pancreas
25
HRAS
carcinomas of bladder
26
NRAS
hematopoietic cancer
27
Blocking RAS
blocks proliferative response to EGF, PDGF, CSF-1
28
BRAF
member of RAS family
60% of cancers
80% of benign growths
29
BCR-ABL
mutated tyrosine kinase due to translocation
| designer drug imatinib mesylate blocks BCR-ABL kinase
30
MYC
most commonly implicated TF
modulates histones methylation, decreases cell adhesion, increased cell mortality, increased telomerase activity, increased protein synthesis, decreased proteinase, and modulated cell metabolism, possibly interacts with DNA repair mechanism
31
CIP/WAF family
CDKI
broadly block CDKs
p21, p27,p57
32
INK4 family
block specifically cyclin D/CDK4A and cyclin D/CDK6
| p15, p18, p19
33
RB
13q14
active hypophosphorylated state in quiescent cells
inactive hyperphosphorylated state in G1/S transition
controls cell cycle and stability of p27 and involved w/differentiation
34
early G1
RB active and bound to E2F family of TF inhibiting cyclin E
| also recruits chromatin remodeling proteins which bind E2F responsive genes (cyclin E) making them insensative to TFs
35
mitogenic signals
activate cyclin D expression -> cyclin D-CDK4/6 complexes-> complexes phosphorylate RB -> inactive -> progress thru cell cycle
36
M phase
phosphates removed -> RB active
37
mir34
critical for p53 function
38
activators of p53
ATM and ATR
39
MDM2
blocks p53
| released from p53 if DNA damage repair successful
40
p53 collaborators
p63, p73
41
APC
adenomatous polyposis coli genes
tumor suppressors
component of WNT pathway to down regulate beta catenin by complexing with it so it becomes degraded
42
germ line mutations of APC
only 1 mutant allele 1000's of polyps in colon by teens
| gives rise to colon cancer after loss of second allele
43
B catenin
degraded by being bound to APC
also contact inhibited by normal cell connections via E-cadherin
WNT blocks APC complex -> B catenin -> nucleus -> increase c-MYC, and cyclin D1
44
INK4a/ARF
aka CDKN2A
p16/INK4aCDK blocks cyclin D/CDK2
P14/ARF increase p53 by blocking MDM2
45
TGF beta
blocks proliferation
binds serine-threonine kinase complex composed of TGFbetaR I&2-> dimerize -> SMADs translocate to nucleus -> bind SMAD4 -> TF -> increase CDKIs p21 and p15
also blocks c-MYC, CDK2, CDK4, cyclins A and E
100% of pancreatic cancers have mutated TGF beta and 83% of colon cancers
46
PTEN
membrane bound associated phosphatase
inhibits prosurvival/growth PI3K/AKT pathway -> BAD, MDM2, AKT
may be most commonly mutated pathway in human cancers
47
cower syndrome
autosomal dominant
marked by frequent benign growths
increased in epithelial cancers
48
AKT
activated by PTEN
| inactivates TSC1/TSC2 complex
49
TSC1 and TSC2
products of tumor supressor genes which are mutated in tuberous sclerosis
50
tuberous sclerosis
autosomal dominant disorder associated w/development malformations
usually benign neoplasms
inactivation of TSC1/2 unleashes mTOR
mTOR stimulates uptake of nutrients for growth and augments protein synthesis
51
NF1
if mutated develop numerous benign nuerofibromas and optic n gliomas
neurofibromatosis type 1
some become malignant peripheral n sheath tumors
RAS trapped activated
52
NF2
less common then NF1
neurofibromatosis type 2
benign bilateral schwannomas of acoustic n
cannot form normal cell to cell jnx, therefore insensitive to growth arrest signals generated by contact
53
VHL
part of ubiquitan ligase complex
critical substrate is HIF1alpha
in presence of oxygen HIF1alpha is hydroxylated and bound to VHL -> ubiquinated -> degraded
hypoxic -> HIF1 alpha to nucleus -> VEGF, PDGF
54
VHL mutations
renal cancer, pheochrmocytoms, hemangioblastoms of CNS(due to increased erythropoietin produced by tumor), retinal angiomas, renal cysts
55
WT1
wilms tumor -> pediatric kidney cancer
| WT1 protein is transcriptional activator for renal and gonadal differentiation
56
Patched
PTCH1 and 2 tumor suppressor genes encode PATCHED protein which interacts w/hedgehog
regulated by TGFbeta, PDGF
57
mutations in Patched
gorlin syndrome, aka nevoid basal cell carcinoma syndrome
58
evasion of apoptosis
decreased FAS/CD95
increased FLIP (binds death domain, cannot activate caspase8)
BCL2- overexpressed by translocation w/IgH genes
mutated p53 -> increase BAX
59
Mutations which increase VEGF
RAS, MYC
60
vascular dissemination and homing of tumor cells
use CD44 adhesion molecule to migrate to lymphoid tissue
61
metastases blocked by
mir335
| mir126
62
metastases increased by
mir10b
63
metastases oncogenes
SNAIL, TWIST
| usually promote epithelium to mesenchymal transition (EMT)
64
hnpcc
```
hereditary non-polyposis colon cancer syndromj
familial carcinoms of colon
defects in gene mismatch
microsatellite instabilites
germ line mutations in MSH2 and MLH1
```
65
xeroderma pigmentosum
increased risk for development of skin cancers
| loss of nucleotide excision repair
66
diseases w/defects in DNA repair by homologous recombinations
bloom syndrome, ataxia-telangiectasia, fanconi anemia
hypersenativity to DNA damaging agents
BRCA1&2
67
Warburg effect
tumors utilize glycolysis even in presence of oxygen
68
burkitt lymphoma
movement of MYC closer to IGH
69
mantle cell lymphoma
cycin D over expressed by being placed next to IGH
70
follicular lymphomas
translocation which activated BCL2 gene
71
CML
fusion of C-ABL and BCR -> constitutively activated tyrosine kinase
72
MLL
50+ translocation fusions creating TFs
73
fusions
usually inhibit tumor supressors
74
prostate adenocarcinmoas have what fusions
TMPRSS2
| ET family TFs
75
amplified genes
lack normal banding patterns appear homogenous in G-banded karyotypes
76
N-MYC
gene amplification
neuroblastoma
poor prognosis
77
ERBB2
gene amplification
breast cancer
will probably respond well to Ab therapy
78
EZH2
implicated in epigenetic changes
79
CYP1A1
codes for enzyme in cytochrome p-450
| light smokers with this genotype 7x increased risk of lung cancer then other smokers
80
Aflatoxin beta 1
targets p53
81
HTLV-1
```
human T cell leukemia virus type 1
epidemic in japan and carribean
CD4 cells
does not contain nor integrate near oncogenes
Tax gene
```
82
TAX proteins
activate proliferation genes
blocks p16 while increasing cyclins
activates NF-kB -> prosurvival and antiapoptotic genes
also interferes w/DNA repair
83
HPV
benign squamous papillomas
84
which HPV strands are most implicated w/ cancer and what type of cancer
16&18
| squamous cell carcinoma of cervix and anogenital region
85
pathogenesis of HPV
integration occurs in cancer at randon site
| viral products E6 and E7 increase GFs (these only released if DNA integrated)
86
E7
blocks CDKIs and activates cyclins
87
E6
degrades p53 and BAX and activates telomerase
| p53 ARG72 much more susceptible to p53
88
EBV associated cancers
african form of burkitt lymphoma, B cell lymphomas in immuosupressed, subset of hodgkin lymphoma, gastric carcinomas, rare T cell and NK cell lymphoma
89
EBV pathogenesis
uses CD21R to attach to B cell
latent infection, but immortalizes cells
releases LMP1, EBNA2, vIL-10
90
LMP1
from EBV viron
acts on oncogene behaving lie constituently activated CD40R which stimulates B cells
also blocks apoptosis by BCL2
91
EBNA2
from EBV viron
mimics constituently active NotchR
increases cyclin D and SRC family of proto-oncogenes
92
v-IL10
from EBV viron
| blocks macrophages and monocytes from activating T cells
93
Burkitt lymphoma
90% of african tumors carry EBV genome, but only found in 15-20% else where
african form does not express LMP1 or EBNA2
94
nasopharyngeal cancers
100% contain EBV DNA
95
Heliobacter
uses CagA gene to penetrate into gastric epithelium and mimic GFs
96
cushings syndrome
increased pro-opiomelanocortins and corticotropins
97
PSA
prostatic carcinoma
98
CEA
colon, pancreas, stomach, breast
99
AEP
hepatocellullar carcinomas, yolk cell carcinomas
100
CA125
ovarian cancer
101
IGs
multiple myelomas
