Neoplasia Flashcards
(120 cards)
1
Q
What is parenchyma?
A
Gives rise to neoplastic cellular component
2
Q
What is stroma?
A
Gives rise to the supportive cellular component (skeleton) upon which parenchyma resides
3
Q
Malignancy in parenchyma =
A
Carcinoma
4
Q
Malignancy in stroma =
A
Sarcoma
5
Q
Benign tumor of mesenchymal origin?
A
Fibroma or lipoma
6
Q
Malignant tumor of mesenchymal origin?
A
Fibrosarcoma or liposarcoma
7
Q
Benign tumor of epithelial lining of glands/ducts?
A
Adenoma, papilloma, cystadenoma
8
Q
Malignant tumor of epithelial lining of glands/ducts?
A
Adenocarcinoma, papillary carcinoma, cystadenocarcinoma
9
Q
Describe mixed tumor
A
Can be benign or malignant… come from ONE germ cell layer (but have more than one type of neoplastic cell type)
10
Q
Describe teratoma
A
More than one neoplastic cell type from MORE THAN ONE germ cell layer
11
Q
How do tumor cells get their start?
A
They are all derived from the same single founding transformed cell (its a stem cell)
(comes to clinical attention after it has already divided many times)
12
Q
4 types of regulatory genes affected in cancers
A
- Growth-promoting proto-oncogenes
- Growth-inhibiting tumor suppressor genes
- Genes regulating apoptosis
- DNA-repair genes
13
Q
What does DNA methylation do?
A
Silences gene expression
14
Q
What does histone modification do?
A
Either enhances or dampens gene expression
15
Q
PDGF-b chain
POG: PDGFB
A
MoA: Overexpression
Astrocytoma
16
Q
Fibroblast growth factors
POG: HST1
A
MoA: Overexpression
Osteosarcoma
17
Q
Fibroblast growth factors
POG: FGF3
A
MoA: Amplification
Stomach, Bladder, Breast cancer + melanoma
18
Q
TGF-a
POG: TGFA
A
MoA: Overexpression
Astrocytoma
19
Q
HGF
POG: HGF
A
MoA: Overexpression
Hepatocellular carcinoma + thyroid cancer
20
Q
EGF receptor family
POG: ERBB1 (EGFR)
A
MoA: Mutation
Adenocarcinoma of lung
21
Q
EGF receptor family
POG: ERBB2 (HER)
A
MoA: Amplification
Breast carcinoma
22
Q
ALK receptor
POG: ALK
(2 MoAs)
A
MoA: Translocation, fusion gene formation
Adenocarcinoma of lung, lymphomas
MoA: Point mutation
Neuroblastoma
23
Q
GTP-binding proteins
A
KRAS, NRAS, HRAS, GNAQ, GNAS
24
Q
POG: KRAS
A
MoA: Point Mutation Colon, lung and pancreatic tumors 90% pancreatic adenocarcinomas/cholangiocarcinomas 50% colon cancers 30% lung adenocarcinomas
25
POG: HRAS
MoA: Point Mutation
| Bladder and kidney tumors
26
POG: NRAS
MoA: Point Mutation
Melanomas and hematologic malignancies
30% myeloid leukemias
27
POG: GNAQ
MoA: Point Mutation
| Uveal melanoma
28
POG: GNAS
MoA: Point Mutation
| Pituitary adenoma and other endocrine tumors
29
Nonreceptor TK
POG: ABL
(2 MoAs)
MoA: Translocation
CML
MoA: Point Mutation
ALL
30
RAS signal transduction
| POG: BRAF
MoA: Point Mutation/translocation
Melanomas (60%), leukemias, colon carcinoma, others
100% hairy cell leukemias
31
What is BRAF?
Serine/threonine protein kinase sitting atop cascade of other serine/threonine kinases of MAPK family
32
Function of hedgehog pathway?
Major path transmitting info to embryonic cells for proper differentiation
33
Pathologies linked to hedgehog pathway?
- Holoprosencephaly and cyclopia
| - Many cancers
34
Cancers associated w/ hedgehog pathway?
- BCC (most common cancer dx)
- Brain
- Lung
- Mammary gland
- Prostate
- Skin
35
Mechanism of development of hedgehog cancers?
- Adult stem cells transformed into cancer stem cells
36
Relationship of WNT to HH?
Signal transduction pathways that are similar, but distinct from HH
37
Cancers associated w/ Beckwith-Wiedemann syndrome?
- Wilms tumor
- Hepatoblastoma
- Pancreatoblastoma
- Adrenocortical tumors
- Rhabdomyosarcomas
38
What 2 pathways are medulloblastomas associated with?
- WNT and SHH
39
Transcriptional activators
| POG: MYC
MoA: Translocation
| Burkitt's lymphoma
40
Transcriptional activators
| POG: NMYC
MoA: Amplification
| Neuroblastoma
41
What does MYC do?
Activates many genes involved w/ cell growth
| - It is rapidly and transiently induced by RAS/MAPK
42
Function of CDK; D cyclins
Phosphorylates RB, thus allowing it to progress through G1
43
Function of CIP/KIP (p21 and p27)
Block cell cycle by binding CDK-cyclin complexes
44
What induces p21?
p53
45
What does p27 respond to?
Growth suppressors, like TGF-b
46
Function of INK4/ARF family (CDKN2A-C)
| specifically INK4
p16/INK4 binds cyclin D-CDK4 and promotes inhibitory effects of RB
47
Function of INK4/ARF family (CDKN2A-C)
| specifically ARF
p14/ARF increases p53 levels by inhibiting MDM2 activity
48
What does RB do?
Binds E2F Tfs in hypophosphorylated state (PREVENTS G1-S transition)
49
What does p53 do?
- Acts via p21 to arrest cell cycle
- Induces apoptosis by inducing transcription of pro-apop. genes (BAX)
- MDM2 negatively regulates via feedback loop
* Required for G1-S transition
50
APC
| Adenomatous polyposis coli protein
Fxn: Inhibitor of WNT signaling
Familial: familial colonic polyps and carcinomas
Sporadic: stomach, colon, pancreas carcinoma + melanoma
51
NF1
| Neurofibromin-1
Fxn: Inhibitor of RAS/MAPK signaling
Familial: Neurofibromatosis 1 (neurofibromas and malignant peripheral nerve sheath tumors)
Sporadic: neuroblastoma, juvenile myeloid leukemia
52
NF2
| merlin
Fxn: cytoskeletal stability and Hippo signaling pathway
Fam: Neurofibromatosis 2 (acoustic schwannomas and meningiomas)
Sporadic: Schwannoma and meningioma
53
PTCH
| patched
Fxn: Inhibitor of HH signaling
Fam: Gorlin syndrome (BCC, MB, several benign tumors)
Sp: BCC, MB
54
PTEN
| phosphatase and tensin homologue
Fxn: Inhibitor of PIK3/AKT signaling
Fam: Cowden syndrome (variety of benign skin, CNS, GI growths + breast, endometrial and thyroid carcinomas)
Sp: Diverse cancers (carcinomas and lymphoid tumors)
55
SMAD2, SMAD4
Fxn: Component of TGF-b signaling pathway (repressors of MYC and CDK4 exp. and inducers of CDK inhibition)
Fam: Juvenile polyposis
Sp: Colonic and pancreatic carcinomas
56
RB
Fxn: Inhibitor of G1/S transition
Fam: familial retinoblastoma syndrome (retinoblastoma and osteosarcoma)
Sp: retinoblastoma, osteosarcoma and carcinomas of lung, colon, breast
57
CDKN2A
| p14/ARF and p16/INK4
Fxn: p14 is indirect activator of p53 and p16 is negative regulator of CDK
Fam: familial melanoma
Sp: pancreatic, breast and esophageal carcinoma
58
VHL
| von Hippel Lindau protein
Fxn: Inhibitor of hypoxia induced Tfs (HIF1a)
Fam: Von Hippel Lindau syndrome (cerebellar hemangioblastoma, retinal angioma, renal cell carcinoma)
Sp: RCC
59
CDH1
| E-cadherin
Fxn: Cell adhesion, inhibition of cell motility
Fam: familial gastric cancer
Sp: gastric carcinoma and lobular breast carcinoma
60
TP53
Fxn: cell cycle arrest and apoptosis d/t DNA damage
Fam: Li-Fraumeni
Sp: almost all cancers
61
BRCA1/BRCA2
Fxn: repair of ds-DNA breaks
Fam: familial breast/ovarian carcinomas, male breast cancer + chronic lymphocytic leukemia (BRCA2)
62
MSH2, MLH1, MSH6
Fxn: DNA mismatch repair
Fam: hereditary nonpolyposis colon carcinoma
Sp: colonic and endometrial carcinomas
63
WT1
Fxn: Tf
| Familial Wilms tumor
64
MEN1
| menin
Fxn: Tf
| Multiple Endocrine Neoplasia-1 (PT, pituitary and pancreatic tumors)
65
How is normal cell cycle regulation lost?
Loss of one of 4 key regulators:
1. p16/INK4
2. Cyclin D
3. CDK4
4. RB
66
How does HPV harm RB?
E7 binds Rb, not allowing E2F to bind Rb, thus E2F is able to cause cell cycle progression
67
Where is p53 located?
17p13.1
68
Where is RB located?
13q14
69
Cancers with wild-type p53?
- Testicular teratocarcinomas
| - Childhood ALL
70
Cancers with mutated p53?
- Lung and colorectal cancers
71
How does HPV harm p53?
E6 binds p53 and causes its degradation
72
Most common cancers in Li-Fraumeni?
- Sarcomas
- Breast cancer
- Leukemias
- Brain tumors
- Carcinomas of adrenal cortex
73
What's interesting about cancers associated with WT1?
- in Wilms tumor, WT1 acts as tumor suppressor (thus it is down regulated in Wilms tumor)
- in leukemias and breast cancers, it is overexpressed (acting as a proto-oncogene here)
* d/t changes in epigenetics
74
Translocation for CML?
(9;22)(q34;q11)
75
Gene for CML?
ABL 9q34
| BCR 22q11
76
Translocation for AML?
(8;21)(q22;q22)
| 15;17)(q22;q21
77
Translocation for Burkitt lymphoma
(8;14)(q24;q32)
78
Translocation for mantle cell lymphoma
(11;14)(q13;q32)
79
Translocation for follicular lymphoma
(14;18)(q32;q21)
80
What do microRNAs (miRs) do?
Mediate sequence-specific inhibition of mRNA translation via RNA-induced silencing complex
81
What do long noncoding RNAs do?
Modulate gene expression
82
DNMT3A gene
Fxn: DNA methylation
Tumor: AML (20%)
83
MLL1 gene
Fxn: histone modification
Tumor: AL in infants (90%)
84
MLL2 gene
Fxn: histone modification
Tumor: Follicular lymphoma (90%)
85
CREBBP/EP300
Fxn: histone acetylation
Tumor: diffuse large B cell lymphoma (40%)
86
ARID1A
Fxn: Nucleosome positioning/chromatin remodeling
Tumor: Ovarian clear cell carcinoma (60%) and endometrial carcinoma (30-40%)
87
SNF5
Fxn: Nucleosome positioning/chromatin remodeling
Tumor: malignant rhabdoid tumor (100%)
88
PBRM1
Fxn: Nucleosome positioning/chromatin remodeling
Tumor: renal carcinoma (30%)
89
HTLV-1
- T cell leukemia/lymphoma
| Encodes Tax protein, which turns on pro-survival pathways (PI3K/AKT, NFKB) leading to polyclonal T cell expansion
90
EBV
Burkitt lymphoma, B cell lymphomas in T-cell immunosuppressed pts.
*also nasopharyngeal carcinoma (China/Africa)
91
HBV and HCV
- hepatocellular carcinomas d/t chronic inflammation and hepatocellular injury
92
MCV (Merkel cell polyomarvirus)
- Merkel cell carcinoma (skin cancer)
93
HHV-8
Kaposi sarcoma
94
H pylori
Gastric adenocarcinoma and MALT lymphomas
95
Cushing syndrome associated cancers
- Small cell carcinoma of lung
- Pancreatic carcinoma
- Neural tumors
* via ACTH
96
SIADH associated cancers
- Small cell carcinoma of lung
- Intracranial neoplasias
* via ADH or ANP
97
Hypercalcemia
- Squamous cell carcinoma of lung
- Breast carcinoma
- Renal carcinoma
- Adult T-cell leukemia/lymphoma
* via PTHRP, TGFa, IL-1
98
Hypoglycemia
- Ovarian carcinoma
- Fibrosarcoma
- Mesenchymal sarcomas
* via insulin
99
Polycythemia
- Renal carcinoma
- Cerebellar hemangioma
- Hepatocellular carcinoma
* via erythropoietin
100
Myasthenia
- Bronchogenic carcinoma
- Thymic neoplasms
* Immunologic
101
Acanthosis nigricans
- Gastric carcinoma
- Lung carcinoma
- Uterine carcinoma
* Immunologic/EGF
102
Hypertrophic osteoarthropathy/clubbing of fingers
- Bronchogenic carcinoma
- Thymic neoplasms
* Unknown cause
103
DIC
- Acute promyelocytic leukemia
- Prostate carcinoma
* tumor factors activating clotting
104
Venous thrombosis
- Pancreatic carcinoma
- Bronchogenic carcinoma
* Tumor products (mucins activating clotting)
105
HCG associated cancers
- Trophoblastic tumors, nonseminomatous testicular tumors
106
Calcitonin associated cancers
- Medullary carcinoma of thyroid
107
Catecholamine and metabolites associated cancers
- Pheochromocytoma
108
a-fetoprotein associated cancers
- Liver cell cancer
| - Nonseminomatous germ cell tumors of testicle
109
Carcinoembryonic antigen associated cancers
- Carcinomas of colon, pancreas, lung, stomach and heart
110
Prostatic acid phosphatase associated cancers
- Prostate cancer
111
Neuron-specifc enolase associated cancers
- Small cell cancer of lung
| - Neuroblastoma
112
Igs associated cancers
- Multiple myeloma and other gammopathies
113
CA-125 mucin associated cancers
Ovarian cancer
114
CA-19-9 mucin associated cancers
Colon, pancreatic cancers
115
CA-15-3 mucin associated cancers
Breast cancer
116
TP53, APC, RAS mutants in stool/serum
Colon cancer
117
TP53, RAS mutants in stool/serum
Pancreatic cancer
118
TP53, RAS mutants in sputum and serum
Lung cancer
119
TP53 mutants in urine
Bladder cancer
120
What are tumor markers best used for?
- Detecting recurrences
| - lack specificity and sensitivity for early detection
