Neoplasia Flashcards
1
Q
What are the most common primary tumors/cancers?
A
Skin, Lung, Large Bowel, Breast, Prostate
2
Q
What is the most common lung cancers?
A
Lung Adenocarcinoma, SCC, Small Cell, Large Cell,
3
Q
What is the difference between a Mixed Tumor and a Teratoma?
A
Mixed Tumor – is from the same germ line (ie. Ectoderm) – common in salivary glands
Teratoma – all 3 germ layers
4
Q
Parenchyma (if malignant) is generally associated with what??
A
Carcinomas
5
Q
The Stroma (if malignant) is generally associated with what??
A
Sarcomas
6
Q
What characterizes Atypia?
A
Small Cytoplasm, Multiple Nuclei, Multiple and Large Nucleoli, Coarse Chromatin
7
Q
Where in the histological image do Neoplasia ALWAYS BEGIN?
A
They begin near the basement membrane, from undifferentiated cells (NEVER DE-DIFFERENTIATED ADULT CELLS)
8
Q
“Differentiation” in Benign vs. Malignant tumors?
A
Benign – well differentiated
Malignant – anaplasia (un-differentiated)
9
Q
What are the Cavitary Lung Lesions?
A
Fibro-Caseous Cavitary TB
Bronchogenic Carcinoma
Staphyloccocal Pneumonia
10
Q
What are Fibroma, Lipoma, Chondroma, Osteoma’s all derived from?
A
Connective Tissue dedrivatives
11
Q
What is a Benign vs Malignant blood vessel tumor?
A
Benign – Hemangioma
Malignant – Angiosarcoma
12
Q
What is Benign vs Malignant Brain Covering tumor?
A
Benign – Meningioma
Malignant – Invasive Meningioma
13
Q
What is a Benign vs Malignant mesothelium tumor?
A
Benign – Benign Fibrous Tumor
Malignant – Mesothelioma
14
Q
What are benign vs malignant epi lining of glands or ducts?
A
Benign – Adenoma, Papilloma, Cystadenoma
Malignant – Adenocarcinoma, Papillary Carcinomas, Cystadenocarcinomas
15
Q
What are Benign vs Malignant Respiratory Passage tumors?
A
B: Bronchial Adenoma
M: Bronchogenic Carcinomas
16
Q
What are Benign vs Malignant Liver cell tumors?
A
B: Hepatic Adenoma
M: Hepatocellular Carcinoma
17
Q
What are Benign vs Malignant Urinary Tract Epi?
A
B: Transitional Cell Papilloma
M: Trasitional Cell Carcinoma
18
Q
What are Benign vs Malignant tumors of melanocytes
A
B: Nevus
M: Melanoma
19
Q
What are Benign vs Malignant Placental Epi?
A
B: Hydatidiform Mole
M: Choriocarcinoma
20
Q
What are Malignant Testicular Epi?
A
Seminoma
21
Q
What are Benign vs Malignant Salivary Glands?
A
B: Pleomorphic Adenoma
M: Malignant Mixed Tumor of Salivary Gland Origin
22
Q
What are Malignant Renal Anlage tumors?
A
Wilms Tumor
23
Q
What are Benign vs Malignant Totipotential Cells in gonads?
A
B: Mature Teratoma (dermoid cyst)
M: Immature Teratoma (Teratocarcinoma)
24
Q
What is the pathway of spread (Metastasis)?
A
1) Loosening of Intercellular Inteactions
2) Degradation of ECM
3) Migration down
4) INVASION!?!?
25
What are the most common cancers of Women vs Men?
Women -- Breast, Lung, Colon
Men -- Prostate, Lung, Colon
In developing world:
W: Breast, Cervix, Lung
M: Lung, Stomach, Liver
26
What type of cells are most at risk for accumulating the genetic leasions that lead to carcinogenesis?
Proliferating Cells
27
What is the difference between Morbidity and Mortality?
Morbididty -- is how many people get the diease (are affected)
Mortality -- is how many people die from the disease
28
What infectious Agents are the most epidemologically attributed to cancer?
HPV and EBV
29
What is the most common cancer in adults vs children?
Adults: Carcinomas (most common)
Children: Leukemia (most common), Neuroblastomas, Retinoblastomas
(A nice little review of chapter 10 . . . youre welcome)
30
What is the development of Cancer (stepwise)?
1) An Initiating Mutation
2) Acquire Genomic Instability
3) Acquire your Cancer Hallmarks
4) Than Further Genetic Evolution
(the last two steps can take years to develop)
over time tumors become more aggresive.
as tumors progess you get a tumor cell population that expands, but more of them leave the replicating pool (think about the darwian comparison)
31
What are the 4 classes of regulatory genes? (the principal targets of cancer causing mutations)
1) Proto-oncogenes
2) Tumor Suppresors
3) DNA Repair Mechs
4) Genes that regulate Apoptosis
32
Complementary Mutations occur in a stepwise fashion and result in 3 things?
1) Cancer Hallmarks
2) Driver Mutations
3) LOF mutations
33
Conversion of 1 of the 2 alleses from a proto-oncogene to an oncogene is sufficient to promote neoplasia -- but it requires loss of \_\_\_?
Both Tumor Suppressor alleles to promote neoplasia (as one of the two protein products made is sufficient to inhibit neoplasia
34
What do MiR's do?
They inhibit translation of SELECT specific sequences of mRNA
35
What are some RNA-mediated Modifications?
RNA directed DNA Methylation
RNA interference mediated chromatin remodeling
miRNA (MiR's) etc
36
What are the Hallmarks of Cancer?
1) Self-sufficiency
2) Insesitivity to growth inhibitory signals
3) Altered Cell Met
4) Evasion of Apoptosis
5) Limitless Replication
6) Sustained Angiogenesis
7) Ability to invade and metastasize
8) Ability to evade host defense mechs
37
What tends to accerelarte the features of Hallmarks of Cancer?
Genomic Instability
Cancer Promoting Inflammation
38
How do cancer cells have limitless replicative potential?
1) inactivate senescence
2) reactivate telomerase
(Some of the cells must be able to be stem-cell like -- or this can't occur)
39
What is a Proto-Oncogene?
A normal cell gene whose products promote cell proliferation
40
What is an Oncogene?
is a mutated or overexpressed version of a proto-oncogene that fxns autonomously -- it has lost dep. on normal growth promotion signals
41
What is an Oncoprotein?
Is a protein encoded by an oncogene
42
What are the Fxns of the following?
CDK4/C-D
P21/P27
Rb
P53
CDK4/C-D -- complex that Phosp, RB -- progreses through G1
P21/P27 -- blocks cell cycle, by binding to CDK4/C-D complex
Rb -- binds to E2F in its hypophosp. state -- prevents G1-S transition
P53 -- causes cell cycle arrest -- to fix damage, or to promote apoptosis
43
What negatively inhibits p53?
MDM2
44
What is cancers are implicated in the following?
EGF Recp TK
HER2 Receptor
Jak2 Tyr K
ABL NonReceptor TK
RAS
PI3K/BRAF
Amp of MYC
EGF -- Lung Cancer
HER2 -- Breat Cancer
Jak2 -- Myeloproliferative Disorder
ABL -- Chronic Myelogenous Leukemia and Acute Lymphoblastic Leukemia
RAS -- many cancers
PI3K -- Many cancers
MYC -- Burkitt Lymphoma and Neuroblastoma
45
What are 4 antiproliferative effects of RB in cancers?
LOF mutations in RB
Gene Amp of CDK4/CD
Loss of p16/INK4a (CDK inhibitors)
E7 protein of HPV
46
What is the steps of p53 action?
1) ATM/ATR kinases sense DNA damage
2) they Phosph p53, (MDM2 unbinds it)
3) p53 upregulates CDK inhibitors (p21)
4) cell cycle arrest -- repairs damage or apoptosis
(p53 -- E6 protein of HPV)
47
Li-Fraumeni Syndrome have what problem?
They inherit one defective copy of TP53 and have a high incidence of cancer
48
_Major Tumor Suppressor Genes_
APC
Neg Regulator of WNT (degrades B-Catenin)
in Familial Adenomatous Polyposis (AD)
and Colon Carcinomas
49
_Major Tumor Suppressor Genes_
E-Cadherin
Binds to B-Catenin / growth inhibition of epi cells
Familial Gastric Cancer (AD) -- (CDH1)
50
_Major Tumor Suppressor Genes_
CDKN2A
codes for p16/INK4a --\> inhibits Rb
Familial Melanoma (AD)
51
Major Tumor Suppressor Genes
TGF-B
inhibits cell proliferation in normal tissues
in carcinomas
52
Major Tumor Suppressor Genes
PTEN
Codes for a lipid phosphatase (PI3K/AKT)
Cowden Syndrome (AD) -- which is Breast and Endometrial Carcinoma
53
Major Tumor Suppressor Genes
NF1
Encodes a GTPase --\> neg regulates RAS
Neurofibromatosis Type 1 (AD)
54
Major Tumor Suppressor Genes
NF2
encodes merlin -- cytoskeletal protein
Neurofibromatosis Type 2
55
Major Tumor Suppressor Genes
WTI
TF for develpoing genitourinary tissues
WIlms Tumor
56
Major Tumor Suppressor Genes
PTCH1
encodes membrane receptor -- a neg. regulator of SHH
Gorlin Syndrome (AD) -- BCC and Medulablastoma
57
Major Tumor Suppressor Genes
VHL
Ubiquitin Ligase -- which degrades Hypoxia inducible factor (HIF)
Von Hippel-Lindau Syndrome (AD) -- renal cell carcinoma, and pheochromacytoma
58
Selected Proto-Oncogenes (Mode of activation/ associated human tumor)
EGF Recptor Family
Mutation/Amplification
Mut -- Adenocarcinoma of Lung
Amp -- Breast Carcinoma
59
Selected Proto-Oncogenes (Mode of activation/ associated human tumor)
ALK (receptor tyrosine k)
Translocation, Point Mutation
Adenocarcinoma of lung, Lymphomas, Neuroblastoma
60
Selected Proto-Oncogenes (Mode of activation/ associated human tumor)
RAS/BRAF
Point Mutation/Translocation
Melanomas, Leukemias, Colon Carcinoma
61
Selected Proto-Oncogenes (Mode of activation/ associated human tumor)
ABL (Non-receptor tyrosine kinase)
Translocation -- Chronic Myelongenous Leukemia
Point Mutation -- Acute Lymphonblastic Leukemia
62
Selected Proto-Oncogenes (Mode of activation/ associated human tumor)
MYC
(MYC) Translocation -- Burkitt Lymphoma
(NMYC) Amplfication -- Neuroblastoma
63
Selected Proto-Oncogenes (Mode of activation/ associated human tumor)
ERBB1
ERBB2
ERBB1 -- encodes EGFR -- point mutations in Lung Adenocarcinomas
ERBB2 -- encodes HER2 == point mutations in Breast Carcinomas
64
ABL, NOTFCH1, Jak2 are bigger in what type of cancers?
Leukemias and Lymphomas
65
What are the Three RAS genes in humans?
where were they discovered?
HRAS, KRAS, NRAS
were discovered in transforming retrovirsues
66
What Carcinomas are RAS mutations more frequent?
Pancreatic Adenocarcinomas
Cholangiocarcinomas
Colon, Endometrial and Thyroid Cancers
Lung Adenocarcinomas and Myeloid Leukemias
67
Where are mutations in BRAF more frequent?
Hairy Cell Leukemias
Melanomas
Benign Nevi
others-
68
Disruption of SHH signaling during embryonic development can lead to?
Holoprosencephaly, Cyclopia
69
What is the most common malignant brain tumor in childhood?
Medullablastoma
70
What other cancers are associated (higher risk) for patients with Wilms Tumor?
Hepatoblastoma
Pancreatoblastoma
Adrenocortical Tumors
Rhabdomyosarcomas
71
MYC is known as . . .
and associated with what tumors?
the Major Transcriptional Regulator of Cell Growth
NMYC, and LMYC are paralogs
ASSOCIATED WITH: Burkitt Lymphoma, Neuroblastoma, common carcinomas
Burkitt Lymphoma -- (8:14) translocation
72
What is a paralog?
a gene that is related to another gene by descent from a single ancestral gene -- may have a different DNA seq. and biological fxn
73
Selected Tumor Suppressor Genes: what syndrome/cancer?
Rb
Familial Retinoblastoma
74
Selected Tumor Suppressor Genes: what syndrome/cancer?
TP53
Li-Fraumeni Syndrome
75
Selected Tumor Suppressor Genes: what syndrome/cancer?
MSH
Hereditary Nonpolyposis Colon Carcinoma
76
Selected Tumor Suppressor Genes: what are the associated oncoproteins with each?
APC
NF1
NF2
PTCH
RB
VHL
E-Cadherin
TP53
BRCA1/BRCA2
MSH
WT1
APC -- Adenomatous polyposis coli protein
NF1 -- neurofibromin 1
NF2 -- merlin
PTCH -- Patched
Rb -- Retinoblastoma protein
VHL -- Von Hippel Lindau protein
E-Cadherin -- E-Cadherin
TP53 -- p53 protein
BRCA1-BRCA2 -- Breast Cancer 1/Breast Cancer 2
MSH -- MSH1
WT1 -- WIlms Tumor 1
77
What are the following regarded as?
Tp53
APC
Rb
Tp53 -- Guardian of the Genome
APC -- Gatekeeper of colonic neoplasia
Rb -- Governor of the cell cycle
78
What HPV proteins associate with the following?
TP53
RB
TP 53 -- E6
RB -- E7
79
How many hits and on what chromosome does it take to produce retinoblastoma?
It takes 2 Hits to the 13q14 chromosome to produce retinoblastoma
(Familial vs Sporadic cases)
80
What are the 4 key regulators of the Cell cycle?
P16/INK4a
Cyclin D
CDK4
Rb
81
How does HPV E7 protein cause oncogenesis in humans?
E7 binds to hypophosphorylated Rb and detaches it from E2F -- allowing E2F to bind and cause cell cycle progression
(E7 has a high affinity for Rb)
82
Tp53 is on what chromosome?
and can inhibit what?
17p13.1
angiogenesis
83
Where is the WT1 Gene located?
11p13
regulates the mesenchymal to epi transition of kidney developement . . . causes Wilms Tumor
84
How do tumor cells cause evasion?
By expressing PD-LI -- which binds to PD-1
causes evasion of the immune systrem (one of the hallmarks of cancer)
Monoclonal Abs target this
85
How does CTLA4 play in cancer cells?
It can act as an off swithc when bound to CD80/86 on the surface of APC.
It has serious side affects when targeted by drugs -- better to target PD-L1\*\*
86
Wat Key enzme is involved in modulation production of inflammtory mediators by immune cells?
PDE4 (Phosphodiesterase 4) -- degrades cAMP
87
Psoriasis patients have an increased risk of what cancer?
Non-Melanoma SKin Cancer
IE: BCC, SCC etc.
88
How is vascularization of tumors controled?
What specific factors regulate it?
A Balance of Angiogenic and Anti-Angiogenic factors produced by tumor and stromal cells
P53, -- inhibits it
RAS, MYC, MAPL, -- upregulate VEGF --\> promotes it
89
What is the first metastatic site that tumors can be predicted to go to?
Capillary Beds -- mainly Liver, Lungs
90
When talking about metastasis, what is organ tropism?
Tropism -- is because of expression of certain receptors on tumor cells that fit with ligands on certain organs -- which is why we see the cancer spread there.
91
What is Dormancy?
Is when a tumor cell has "gone quiet"
Like a leopord in the jungle awaiting to attack its prey. . . . .
92
What are Oncofetal Ags?
They are proteins that are normally only found during fetal development -- but show up in cancers of adults
93
Genomic Instability:
HNPCC syndrome have defects in:
Xeroderma Pigmentosum have defects in:
Bloom Syndrome, Ataxia-Telangiectasia, Fanconi Anemia are hypersensitive to?
BRCA1/BRCA2:
RAG1,RAG2, AID:
HNPCC -- defects in mismatch repair system
XP -- defefcts in nucleotide excision repair system -- pyrimidine dimers
BS, AT, FA -- hypersensitive to DNA Damaging agents -- ionizing radiation
BRCA's -- Breast Cancer
RAG -- lymphoid neoplams
94
What are cancer-enabling effects of inflammatory cells and resident stromal cells?
Release of factors that promote proliferation
Removal of Growth Suppresors
Enhanced resistance to cell death
Angiogenesis
Invasion and Metastasis
Evading Immune Destruction
95
Note: Anemia, Fatigue, vs Cachexia
ANemia -- low BC count -- low oxygen levels
Fatigue -- low energy levels due to anemia and misc
Cachexia -- equal loss of protein and fat (due to increased BMR)
96
Oncogenes (Translocations)
Chronic Myelogenous Leukemia
(9:22)(q34:q11)
ABL-- 9q34
BCR -- 22q11
97
Oncogenes (Translocations)
Acute Myeloid Leukemia
(8:21)(q22:q22)
| (15:17)(q22:q21)
98
Oncogenes (Translocations)
Burkitt Lymphoma
(8:14)(q24:q32)
99
Oncogenes (Translocations)
Mantle Cell Lymphoma
(11:14)(q13:q32)
100
Oncogenes (Translocations)
Follicular Lymphoma
(14:18)(q32:q21)
101
What are the difference between miRNA's and LncRNA's?
miRNA's (miR's) -- modulate the translation of specific seq of mRNA
LncRNA's -- (exceed coding mRNAs) they can bind to regions of chromatin, restricting RNA Polymerase access to coding genes within the region
102
Epigenetic Reg Genes -- (Fxn and Tumor)
DNMT3A
DNA Methylation
Acute Myeloid Leukemia
103
Epigenetic Reg Genes -- (Fxn and Tumor)
MLL1
MLL2
MLL1 -- Histone Methyl -- Acute Leukemia in Infants
MLL2 -- Histone Methyl -- Follicular Lymphoma
104
Epigenetic Reg Genes -- (Fxn and Tumor)
CREBBP/EP300
Histone Acetlyation
Diffuse Large B Cell Lymphoma
105
Epigenetic Reg Genes -- (Fxn and Tumor)
ARID1A
Nucleosome/Chromatin Remodeling
Ovarian Clear Cell Carcinoma/Endometrial Carcinoma
106
Epigenetic Reg Genes -- (Fxn and Tumor)
SNF5
Nucleosome/Chromatin Remodeling
Malignant Rhabdoid Tumor
107
Epigenetic Reg Genes -- (Fxn and Tumor)
PBRM1
Nucleosome/Chromatin Remodeling
Renal Carcinoma
108
What are the different Chemical Carcinogens?
Direct-Acting Carcinogens
Indirect-Acting Carcinogens
Promotion of Chemical Carcinogenesis
(through initiation and promoters)
most require metabolic activation to become ultimate carcinogens
109
Nonmelanoma skin cancers are associated with ____ exposure to UV Radiation?
Where as Melanomas are associated with ____ exposure as occurs with sunbathing
Nonmelanoma -- total cumulative exposure to UV radiation
Melanomas -- associated with intense intermittent exposure
110
UVB light causes what?
Formation of Pyrimidine dimers in DNA
-- Meyloid Leukemias, Thryoid Cancer (frequently)
-- Breast, Lungs, Salivary glands (Interm)
111
What is the main Oncogenic RNA Virus?
HTLV-1
112
What are the Oncogenic DNA Viruses?
HPV
EBV (& Burkitt Lymphoma)
HBV/HCV
Merkel Cell Polyomavirus
HHV-8
113
Can a neoplasm (benign or malignant) cause death?
Yes
114
What are Paraneoplastic Syndromes?
they are symptoms that are not explained by the location of the tumor/ or by elaboration of the hormones indigenous to the tissue of location.
115
Paraneoplastic Syndromes
Cushing Syndrome
Small Cell Carcinoma of the Lung
Pancreatic Carcinoma
Neural Tumors
116
Paraneoplastic Syndromes
SIADH
Small Cell Carcinoma of Lung
Intracranial Neoplasms
117
Paraneoplastic Syndromes
Hypercalcemia
Squamous cell carcinoma of lung
Breast and Renal Carcinoma
Adult T- Cell leukemia/lymphoma
118
Paraneoplastic Syndromes
Hypoglycemia
Ovarian Carcinoma
Fibrosarcoma
(Mesenchymal sarcomas)
119
Paraneoplastic Syndromes
Myathenia (Nerve and Muscle)
Bronchogenic Carcinoma
Thymic Neoplams
120
Paraneoplastic Syndromes
Acanthosis Nigricans
Gastric Carcinoma
Lung Carcinoma
Uterine Carcinoma
121
Paraneoplastic Syndromes
Hypertrophic Osteoarthropathy (and clubbing of fingers)
Bronchogenic Carcinoma
Thymic Neoplasms
122
What is Migratory Thromboplebitis (Trousseau Syndrome)
DIC (Disseminated Intravascular Coagulation)
MT: it can be encoutered due to deep-seated cancers: Pancreatic or Lung Carcinomas
DIC: is associated with APML (Acute Promyelocytic Leukemia) and Prostatic Adenocarcinoma
123
What is Grading vs Staging of a tumor?
Grading -- is based on the degree of differentiation
Staging -- is due to size, LN spread, and malignancy
(We care more about Staging diagnosis)
124
Immunohistochemistry
- list the different histochemicals
Cytokeratin
EMA (EPithelial Membrane Ag)
LCA (CD45) (Leukocyte Common Ag)
Peroxidase
Non-Specific Esterase
GFAP (Glial Fibrillary Acidic Protein)
125
In medicine we have gone from treating the organ to a molecular target - name the targets.
Lung
Breast
Prostate
Colon
Brain
Lung -- Mutated KIT
Breast -- Mutated HER2
Prostate -- Mutated EGFR
Colon -- Mutated BRAF
Brain -- Mutated PI3K
126
What is Chromothripsis?
It is a single catastrophic event that leads to MULTIPLE double-stranded breaks in DNA
It is repaired by error prone mechanisms -- and can lead to tumors/cancers
127
Note Table 7-12 Selected Tumor Markers
128
Carcinoembryonic Ag (CEA) is found in what?
Alpha-Fetal Protein?
Carcinomas of the Colon, Pancreas, Stomach, Breast
produced in Hepatocellular Carcinomas, Teratocarcinomas, yolk sac stuff, embryonal cell carcinomas
129
PSA, CEA, AFP lack both specificty and sensitivity required for?
Early Detection of cancers -- and are good for detection of recurrences.
