Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pathology 1 Block 2 > Neoplasia 3: Molecular Basis > Flashcards

Neoplasia 3: Molecular Basis Flashcards

1
Q

what are the 8 steps that lead to the essential alteration that lead to malignant transformation?

A
  1. cell begins making its own growth signals
  2. cell becomes insensitive to growth inhibition signals
  3. cellular metabolism altered
  4. apoptosis is evaded
  5. limitless replication
  6. sustained angiogenesis
  7. ability to invade (metastasize)
  8. immunity evasion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is the Warberg effect?

A

cancer cells keep a high glucose uptake even when in too much presense of O2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What does it mean that cells produce their own growth signals?

A

it means that cells have proto-oncogenes that get modified into oncogenes in order to make oncoproteins which allows the production of growth factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what do proto-oncogenes do?

A

Synthesis of growth factors, growth factor receptors, signal transducers, transcription factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

a mutation of a proto-oncogene will affect what?

A
  1. Growth factors
  2. Growth factor receptors
  3. Signal transducing proteins
  4. Transcription factors
  5. Cyclins & cyclin dependent kinases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

give an example of a growth factor?

and a growth factor receptor?

A

PDGF

PDGFR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

give an example of a proto-oncogene?

A

SIS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is an example of a mutation that may cause tumor growth factor receptor activation?

A

point mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

a point mutation in RET (protooncogene) can be seen in what diseases?

A

MEN (Multiple Endocrine Neoplasia) type 2A, 2B adn familial medullary carcinoma of the thyroid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

a point mutation in c-KIT can be seen in what disease?

A

GIST (gastroinestinal stromal tumor)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

a point mutation in FLT3 gene can be seen in what disease?

A

myeloid leukemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

a point mutation in RAS can be seen in what disease?

A

pancreatic adenocarcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

through what 3 characteristics do we identify MEN 1?

A

1) Primary hyperparathyroidism
2) Endocrine tumors of the pancreas
3) pituitary prolactinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

MEN 2 is subclassified into what 3 syndromes?

A

1) MEN-2A
2) MEN-2B
3) familial medullary thyroid cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is MEN 2A? (other name)

what symptoms will you see?

A

sipple syndrome

you will have: pheochromocytoma, medullary carcinoma of the thyroid, and parathyroid hyperplasia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what type of mutation occurs in MEN 2A?

A

germline gain-of-functoin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

a point mutation in ALK gene can be seen in what disease?

A

lymphomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

in what disease do we see overexpression a gene?

A

ERBB1 - lung adenocarcinoma

ERBB2 - in breast cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what disease is this?

A

GIST

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what is this?

A

GIST

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what is the immunohistochemistry used for GIST?

A

c-kit (looks brown)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

point mutation of what gene familly is the most common type of abnormality involving proto-oncogenes in human tumors?

A

ras gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what genes make up the RAS family?

A

HRAS

KRAS

NRAS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

in what cancers is the RAS point mutation the highest (90%)?

A

pancreatic adenocarcinoma

cholangiocarcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
in what cancers is the RAS point mutation 50% higher?
colon endometrial thyroid cancer
26
RAS stimulates what 2 receptor tyrosine kinase?
MAPK IP3/AKT
27
what is this?
adenocarcinoma of colon
28
what is this?
adenocarcinoma of colon
29
how do you describe adenocarcinoma of colon?
ulceroproliferative lesion
30
BRAF is part of what gene family?
RAF
31
mutations in BRAF are seen in what cancer?
hairy cell leukemia and melanoma
32
JAK/STAT point mutation occurs where? JAK/STAT activation thru’ point mutation seen in what disorders? give example of these disorders?
occurs in JAK 2 myeloproliferative disorders: - polycythemia - 1ry myelofibrosis
33
JAK/STAT point mutation is what type of alteration on tyrosine kinase?
non-receptor tyrosine kinase
34
in what diseases do we see alterations in non-receptor tyrosine kinase?
Chronic Myeloid Leukemia (CLL) Acute Lymphoblastic Leukemia (ALL)
35
how do we get oncogenic BCR-ABL tyrosine kinase? What is bad with BCR-ABL oncogene?
when C-ABL gets translocated from Ch. 9 to BCR region of Ch. 22 this chimeric gene is always active causing increase activity of ABL tyrosine kinase
36
what inhibits BCR-ABL tyrosine kinase?
imatinib mesylate
37
transcription factors include which products of proto-oncogenes?
MYC, MYB, JUN, FOS, and REL
38
what transcription factor is most commonly involved in human tumors?
myc
39
what is the genetic basis of burkitt lymphoma?
translocations of the MYC gene on chromosome 8 that lead to increased MYC protein levels
40
what is the translocation partner for MYC in burkitts lymphoma?
IgH locus t(8; 14)
41
what is this?
burkitts lymphoma
42
where do we see point mutation in N-MYC?
in neuroblastoma
43
what is the 3rd most common pediatric malignancy?
neuroblastoma
44
where does neuroblastoma originate? where else can it arise from?
in the adrenal glands, neck, pelvis, brain sympathetic ganglion
45
what is a good prognostic indicator of neuroblastoma?
absense of N-MYC amplification
46
What is the histology for neuroblastoma?
(embryonal) undifferentiated appearance = _small round blue cell tumor_
47
what hormones are produced in a neuroblastoma?
catecholamines
48
what is this?
neuroblastoma of the kidney
49
what are CDK's? (cyclin dependant kinases)
control the cell cycle and move it forward by phosphorylating cyclin complexes
50
what are CDK inhibitors?
they stop the cell cycle
51
what stimulates CDK's?
cyclins
52
what type of mutation will cause cyclin D1 to cause cancer? This happens in what cancers?
gain of function Mantle Cell Lymphoma Breast carcinoma Esophageal carcinoma
53
what type of mutation in CDK inhibitors will lead to cancer? give 2 example where this is seen
loss of function germline mutation in p16:CDKN2A = melanomas somatic mutation of p16 = 95% of pancreatic adenocarcinoma
54
what do tumor suppressors do?
stop cell cycle and lead to failure of growth inhibition
55
what are 3 examples of tumor suppressor genes?
RB VHL p53 WT1 APC NF1 CDKN2A NF2 PTEN
56
what happens if you have a oncogene but have a working tumor suppressor gene?
cells become quiescent
57
how many of retinoblastomas occur spontaneously?
60%
58
how many of retinoblastomas occur inherited?
40%
59
what is knudson's two hit mechanism for retinoblastoma?
both normal alleles of RB locus must be inactivated
60
where do we find RB locus?
13q14
61
what disease is this? what is this symptom?
RB leukocoria (cat eye reflex)
62
what is knudson's hypothesis mechanism in familial cases of retinoblastoma?
child is born with 1 defective gene (first hit is in germline) later: 2nd copy of RB gene lost through somatic mutation
63
what is knudson's hypothesis mechanism in sporadic cases of retinoblastoma?
child born with 2 normal RB genes both copies lost through somatic mutations
64
familial cases of RB are more prone to what other malignancy?
osteosarcoma
65
what is this?
retinoblastoma
66
what is this?
retinoblastoma
67
familial retinoblastoma is an example of a mutation occuring where?
germline
68
sporadic retinoblastoma is an example of a mutation occuring where?
somatically
69
what are 4 examples of somatic retinoblastoma?
1. glioblastoma 2. small cell carcinoma of lung 3. breast cancer 4. bladder cancer
70
what is this? how aggresive is it? what may it cause?
astrocytoma = glioblastoma very aggresive may cause hemorrhage
71
what is p53?
is in charge of: - regulating cell cycle progression - dna repair - apoptosis
72
what is the most frequent mutated gene in human cancer?
TP53
73
when tp53 is mutated, it is usually a gain or loss of function?
loss of function
74
what is an example of a disease caused by a germline mutation of p53?
Li Fraumeni
75
li fraumeni will cause what malignancies?
breast cancer brain tumor carcinoma of adrenal cortex
76
tp53 has mutations more common occuring in somatic or germline?
somatic is more common
77
what are the 3 interlocking mechanisms of p53 tumor suppressor gene?
1. Activation of temporary arrest 2. induction of permanent cell arrest 3. triggering apoptosis
78
what are the major roles of APC gene? what is the main function of APC gene?
- controlling cell fate, adhesion, cell polarity during embryonic development - hold β-catenin activity in check
79
APC gene uses what signaling pathway?
WNT
80
what do you get if you have a germline loss-of-function mutation in the APC ?
Familial adenomatous polyposis
81
what is FAP (familial adenomatous polyposis)?
- thousands of adenomatous polyps develop in the colon during their teens or early twenties - 1 or more of these polyps undergoes malignancy causing colon cancer
82
non-familial colorectal carcinomas and sporadic adenomas also show acquired defects involving how many genes?
both APC genes
83
what is this?
familial adenomatous polyposis
84
what is the characteristic feature in carcinomas?
mutation causing e-cadhering loss and increase in ß-catenin
85
how do cells that lose APC gene behave? what is an example of a germline mutation that loses the APC gene? what is an example of a somatic mutation that loses the APC gene?
like they are being continously stimulated by WNT familial adenomatous polyposis hepatoblastomas, hepatocellular carcinomas
86
what causes FAP? how are 75% of cases of FAP acquired? how many polyps are needed in order to diagnose? at what age is FAP diagnosed?
mutation of APC gene inherited 100 30-50
87
CDKN2A encodes for 2 proteins
1) p16/INK4a 2) p14/ARF
88
what is p16/INK4? what does it do?
* cyclin dependant kinase inhibitor * blocks CDK4/cyclin D-mediated phosphorylation of RB - It reinforces RB checkpoint
89
with what disease is CDKN2A mutation of the germline associated? ## Footnote with what disease is CDKN2A sporadic mutation associated?
Familial Melanoma bladder cancers, head and neck cancers, cholangiocarcinomas, and ALL
90
_what is the TGF-ß pathway_ TGF-ß inhibits what? how does it control it? what happens after? how do the cellular signals differ when normal and when in cancer?
cell proliferation by binding to TGF-ß receptro 1 and 2 activates SMAD proteins for cellular signals normal = signal for anti-proliferative cancer = no anti-proliferative effect through loss of function
91
what diseases can be found or caused by a mutation of type 2 TGF-ß receptor?
colon cancer stomach cancer edometrial cancer
92
mutational inactivation of SMAD4 is common in what cancer?
pancreatic cancer
93
in what disease is PTEN mutated? PTEN mutation causes what? PTEN increases what types of cancer?
Cowden syndrome frequent benign growths (skin appendage tumors) breast, endometrial, thyroid
94
what is this picture?
endometrial carcinoma due to PTEN mutation
95
endometrial cancers are divided into what 2 categories? Which category is the most common? what condition predisposes to each category? what gene mutation predisposes to endometrial cancer?
type 1 and 2 type 1 type 1 = endometrial hyperplasia type 2 = endometrial atrophy type 1 = PTEN type 2 = TP53
96
what protein defect is found in neurofibromatosis 1? what is the funciton of this protein? what patient with neurofibromatosis 1 develops benign neurofibromas? what are the clinical features of neurofibromatosis 1?
neurofibrin 1 downregulation of the RAS signal transduction pathway (tumor suppresor) those with 1 inherited mutant allele symptoms: cafe-au-lait, lisch nodules (hamartomas in iris), neurofibroma
97
what disease is this? what is this?
neurofibromatosis neurofibroma
98
what disease is this? what is this?
neurofibromatosis lisch nodules
99
what disease is this? what is this?
neurofibromatosis cafe au lait spots
100
how do you get neurofibromatsis 2? what is the classical presentation? what happens if you have a sporadic mutation on both alleles?
germline mutation of neurofibrin 2 symptoms: benign bilateral schwannomas of the acoustic nerve (in skull) - you see deafness and paralyzed you will see sporadic meningiomas and ependymoma
101
how does von Hippel-Lindau get mutated? this can lead to what cancer? when in life does this mutation occur or cancer occur? what type of mutation will lead to the cancer? what transcription factor gets degraded?
chromosome 3p hereditary renal cancer, pheochromocytoma, hemangioblastoma of CNS late in life loss of function HIF1alpha
102
what is this? what is it associated with?
renal carcinoma mutation of von hippel-lindau
103
what cell compose a pheochromocytoma? what do these cells produce? what is the rule of 10? what are the clinical features of pheochromocytoma?
chromaffin cells catecholamines they are: 10% of sporadic are bilateral 10% are malignant 10% are not associated with hypertension clinical features: hypertension, sweating, palpitation, tremor paroxysmal episodes: abrupt elevation of BP
104
what will lab work show for pheochromocytoma?
elevated urinary excretion of free: vanillylmandelic acid and metanephrines
105
what is this?
pheochromocytoma
106
where is Wilms tumor suppressor gene located? What does Wilm's tumor cause? in what age group do we see it? WT1 protein is used for what?
Ch. 11p13 Wilm's tumor its pediatric activates genes for renal and gonadal differentiation
107
what is this?
wilms tumor
108
what is BCL-2? what is an example of a cancer that overexpresses BCL-2? what is the translocation of this cancer?
anti-apoptotic factor B cell lymphoma (follicular lymphoma) t(14;18)
109
true or false all cancers have immortal cells? telomerase activity is not seen in all tumor cells?
true false
110
what are the 3 factors that lead to immortality of cancer cells?
1. evasion of senescense 2. evasion of mitotic crisis 3. capacity for self-renewal
111
in cancer, there is neovascularization, what is this? what is the purpose of neovascularization?
new vessels get formed from previously existing capillaries It helps the tumor: - provides nutrients - new endothelial cells secrete growth factors - secrete VEGF, BFGF for angiogenesis
112
mortality due to cancer is mostly due to what? what are the 2 metastatic cascades of metastasis?
metastasis 1) invasion of ECM 2) vascular spreading, colonization
113
what must happen for a tumor to invade the ECM?
* basement membrane must be breached * crossing of interstitial connective tissue * invade circulaiton by breaking through basement membrane of blood vessel
114
what are the general steps for a tumor to invade the ECM?
1. tumor detaches from other tumor cells 2. tumor cell arrives ECM 3. ECM degraded 4. tumor cell migrates
115
what holds tumor cells together? how do tumor cells break the basement membrane?
E-cadherins by using MMP
116
in circulation, how do we see tumor cells? once in circulation, what do tumor cells use to adhere to selective sites? prostatic adenocarcinoma favors what anatomical site to spread? bronchogenic carcinoma favors what anatomic location to spread? neuroblastoma favors what anatomic location to spread?
clumped CD44 expressed on T cells bone (mostly vertebral) adrenals and brain liver and bones
117
what is this an example of?
vascular metastasis (tumor emboli)
118
how do tumors evade host defense? what patients have increased risk for developing cancer?
using cell-mediated mechanisms (tumor antigens get presented on cell surface using MHC 1 and get recognized by CD 8+) immunosuppresed
119
_genomic instability_ What are 3 mechanisms in the DNA repair system that can cause cancer?
1) mismatch repair 2) nucleotide excision repair 3) recombination repair
120
what cancer can occur with mismatch DNA repair system? what are the symptoms seen with this cancer? mutation in what genes will lead to this cancer? how do mismatch repair errors lead to mutations predisposing to cancer? In what region do we find most mismatch mutations?
HNPCC symptoms: lesion in proximal colon, no pre-existing colon MSH2 or MLH1 they cause accumulations of many mutations in microsatellite regions
121
what disease is this?
FAP because there are multiple polyps
122
what is this?
HNPCC because there is ulcero-proliferative growth (not polyp)
123
what disease is an example of mutated nucleotide excision repair genes? mutated nucleotide excision repair genes are involved in what type of cancers? what is the mechanism by which this mutated genes cause the skin cancer?
xeroderma pigmentosum skin cancers (squamous cell carcinomas, basal cell carcinomas) UV light causes cross-linking of pyrimidine residues
124
what disorders are associated with recombination repair mutation? what characterizes these disorders?
ataxia-telangiectasia, bloom syndrome, fanconi anemia hypersensitivity to DNA damaging agents: ionizing radiation, DNA crosslinking agents
125
what is the gene mutated in ataxia-telangiectasia? what is the mechanism?
ATM gene ATM gene recognizes DNA double-strand breaks caused by ionizing radiation
126
what is this?
breast cancer (carcinoma of breast)
127
what is this?
breast cancer (carcinoma of breast) note: infiltrating malignant cells
128
mutation of what genes are associated with breast carcinoma (cancer) and ovarian cancer? which gene is related to what cancer? (of the 2 in previous question) what is the normal function of these genes?
BRCA-1, BRCA-2 BRCA-1 = breast/ovarian cancer women prostate cancer = men BRCA-2 = breast cancer in men/women ovarian/prostatic/pancreatic/bile duct cancer transcription regulation & cell cycle control
129
_true of false_ BRCA 1/2 are related to sporadic cases of breast cancer? BRCA-1 is in what Chromosome? BRCA-2 is in what Chromosome?
no, only to familial cancer Ch. 17 Ch. 13

Pathology 1 Block 2 (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions