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MOD Exam 2 > Neoplasia > Flashcards

Neoplasia Flashcards

1
Q

What is parenchyma?

A

Gives rise to neoplastic cellular component

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2
Q

What is stroma?

A

Gives rise to the supportive cellular component (skeleton) upon which parenchyma resides

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3
Q

Malignancy in parenchyma =

A

Carcinoma

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4
Q

Malignancy in stroma =

A

Sarcoma

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5
Q

Benign tumor of mesenchymal origin?

A

Fibroma or lipoma

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6
Q

Malignant tumor of mesenchymal origin?

A

Fibrosarcoma or liposarcoma

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7
Q

Benign tumor of epithelial lining of glands/ducts?

A

Adenoma, papilloma, cystadenoma

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8
Q

Malignant tumor of epithelial lining of glands/ducts?

A

Adenocarcinoma, papillary carcinoma, cystadenocarcinoma

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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)

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10
Q

Describe teratoma

A

More than one neoplastic cell type from MORE THAN ONE germ cell layer

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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)

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12
Q

4 types of regulatory genes affected in cancers

A
  1. Growth-promoting proto-oncogenes
  2. Growth-inhibiting tumor suppressor genes
  3. Genes regulating apoptosis
  4. DNA-repair genes
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13
Q

What does DNA methylation do?

A

Silences gene expression

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14
Q

What does histone modification do?

A

Either enhances or dampens gene expression

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15
Q

PDGF-b chain

POG: PDGFB

A

MoA: Overexpression

Astrocytoma

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16
Q

Fibroblast growth factors

POG: HST1

A

MoA: Overexpression

Osteosarcoma

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17
Q

Fibroblast growth factors

POG: FGF3

A

MoA: Amplification

Stomach, Bladder, Breast cancer + melanoma

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18
Q

TGF-a

POG: TGFA

A

MoA: Overexpression

Astrocytoma

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19
Q

HGF

POG: HGF

A

MoA: Overexpression

Hepatocellular carcinoma + thyroid cancer

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20
Q

EGF receptor family

POG: ERBB1 (EGFR)

A

MoA: Mutation

Adenocarcinoma of lung

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21
Q

EGF receptor family

POG: ERBB2 (HER)

A

MoA: Amplification

Breast carcinoma

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22
Q

ALK receptor
POG: ALK
(2 MoAs)

A

MoA: Translocation, fusion gene formation
Adenocarcinoma of lung, lymphomas

MoA: Point mutation
Neuroblastoma

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23
Q

GTP-binding proteins

A

KRAS, NRAS, HRAS, GNAQ, GNAS

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24
Q

POG: KRAS

A 
MoA: Point Mutation 
Colon, lung and pancreatic tumors
90% pancreatic adenocarcinomas/cholangiocarcinomas
50% colon cancers
30% lung adenocarcinomas
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25
Q

POG: HRAS

A

MoA: Point Mutation

Bladder and kidney tumors

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26
Q

POG: NRAS

A

MoA: Point Mutation
Melanomas and hematologic malignancies
30% myeloid leukemias

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27
Q

POG: GNAQ

A

MoA: Point Mutation

Uveal melanoma

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28
Q

POG: GNAS

A

MoA: Point Mutation

Pituitary adenoma and other endocrine tumors

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29
Q

Nonreceptor TK
POG: ABL
(2 MoAs)

A

MoA: Translocation
CML

MoA: Point Mutation
ALL

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30
Q

RAS signal transduction

POG: BRAF

A

MoA: Point Mutation/translocation
Melanomas (60%), leukemias, colon carcinoma, others
100% hairy cell leukemias

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31
Q

What is BRAF?

A

Serine/threonine protein kinase sitting atop cascade of other serine/threonine kinases of MAPK family

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32
Q

Function of hedgehog pathway?

A

Major path transmitting info to embryonic cells for proper differentiation

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33
Q

Pathologies linked to hedgehog pathway?

A
  • Holoprosencephaly and cyclopia

- Many cancers

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34
Q

Cancers associated w/ hedgehog pathway?

A
  • BCC (most common cancer dx)
  • Brain
  • Lung
  • Mammary gland
  • Prostate
  • Skin
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35
Q

Mechanism of development of hedgehog cancers?

A
  • Adult stem cells transformed into cancer stem cells
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36
Q

Relationship of WNT to HH?

A

Signal transduction pathways that are similar, but distinct from HH

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37
Q

Cancers associated w/ Beckwith-Wiedemann syndrome?

A
  • Wilms tumor
  • Hepatoblastoma
  • Pancreatoblastoma
  • Adrenocortical tumors
  • Rhabdomyosarcomas
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38
Q

What 2 pathways are medulloblastomas associated with?

A
  • WNT and SHH
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39
Q

Transcriptional activators

POG: MYC

A

MoA: Translocation

Burkitt’s lymphoma

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40
Q

Transcriptional activators

POG: NMYC

A

MoA: Amplification

Neuroblastoma

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41
Q

What does MYC do?

A

Activates many genes involved w/ cell growth

- It is rapidly and transiently induced by RAS/MAPK

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42
Q

Function of CDK; D cyclins

A

Phosphorylates RB, thus allowing it to progress through G1

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43
Q

Function of CIP/KIP (p21 and p27)

A

Block cell cycle by binding CDK-cyclin complexes

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44
Q

What induces p21?

A

p53

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45
Q

What does p27 respond to?

A

Growth suppressors, like TGF-b

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46
Q

Function of INK4/ARF family (CDKN2A-C)

specifically INK4

A

p16/INK4 binds cyclin D-CDK4 and promotes inhibitory effects of RB

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47
Q

Function of INK4/ARF family (CDKN2A-C)

specifically ARF

A

p14/ARF increases p53 levels by inhibiting MDM2 activity

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48
Q

What does RB do?

A

Binds E2F Tfs in hypophosphorylated state (PREVENTS G1-S transition)

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49
Q

What does p53 do?

A
  • 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
Q

APC

Adenomatous polyposis coli protein

A

Fxn: Inhibitor of WNT signaling
Familial: familial colonic polyps and carcinomas
Sporadic: stomach, colon, pancreas carcinoma + melanoma

51
Q

NF1

Neurofibromin-1

A

Fxn: Inhibitor of RAS/MAPK signaling
Familial: Neurofibromatosis 1 (neurofibromas and malignant peripheral nerve sheath tumors)
Sporadic: neuroblastoma, juvenile myeloid leukemia

52
Q

NF2

merlin

A

Fxn: cytoskeletal stability and Hippo signaling pathway
Fam: Neurofibromatosis 2 (acoustic schwannomas and meningiomas)
Sporadic: Schwannoma and meningioma

53
Q

PTCH

patched

A

Fxn: Inhibitor of HH signaling
Fam: Gorlin syndrome (BCC, MB, several benign tumors)
Sp: BCC, MB

54
Q

PTEN

phosphatase and tensin homologue

A

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
Q

SMAD2, SMAD4

A

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
Q

RB

A

Fxn: Inhibitor of G1/S transition
Fam: familial retinoblastoma syndrome (retinoblastoma and osteosarcoma)
Sp: retinoblastoma, osteosarcoma and carcinomas of lung, colon, breast

57
Q

CDKN2A

p14/ARF and p16/INK4

A

Fxn: p14 is indirect activator of p53 and p16 is negative regulator of CDK
Fam: familial melanoma
Sp: pancreatic, breast and esophageal carcinoma

58
Q

VHL

von Hippel Lindau protein

A

Fxn: Inhibitor of hypoxia induced Tfs (HIF1a)
Fam: Von Hippel Lindau syndrome (cerebellar hemangioblastoma, retinal angioma, renal cell carcinoma)
Sp: RCC

59
Q

CDH1

E-cadherin

A

Fxn: Cell adhesion, inhibition of cell motility
Fam: familial gastric cancer
Sp: gastric carcinoma and lobular breast carcinoma

60
Q

TP53

A

Fxn: cell cycle arrest and apoptosis d/t DNA damage
Fam: Li-Fraumeni
Sp: almost all cancers

61
Q

BRCA1/BRCA2

A

Fxn: repair of ds-DNA breaks
Fam: familial breast/ovarian carcinomas, male breast cancer + chronic lymphocytic leukemia (BRCA2)

62
Q

MSH2, MLH1, MSH6

A

Fxn: DNA mismatch repair
Fam: hereditary nonpolyposis colon carcinoma
Sp: colonic and endometrial carcinomas

63
Q

WT1

A

Fxn: Tf

Familial Wilms tumor

64
Q

MEN1

menin

A

Fxn: Tf

Multiple Endocrine Neoplasia-1 (PT, pituitary and pancreatic tumors)

65
Q

How is normal cell cycle regulation lost?

A

Loss of one of 4 key regulators:

  1. p16/INK4
  2. Cyclin D
  3. CDK4
  4. RB
66
Q

How does HPV harm RB?

A

E7 binds Rb, not allowing E2F to bind Rb, thus E2F is able to cause cell cycle progression

67
Q

Where is p53 located?

A

17p13.1

68
Q

Where is RB located?

A

13q14

69
Q

Cancers with wild-type p53?

A
  • Testicular teratocarcinomas

- Childhood ALL

70
Q

Cancers with mutated p53?

A
  • Lung and colorectal cancers
71
Q

How does HPV harm p53?

A

E6 binds p53 and causes its degradation

72
Q

Most common cancers in Li-Fraumeni?

A
  • Sarcomas
  • Breast cancer
  • Leukemias
  • Brain tumors
  • Carcinomas of adrenal cortex
73
Q

What’s interesting about cancers associated with WT1?

A
  • 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
Q

Translocation for CML?

A

(9;22)(q34;q11)

75
Q

Gene for CML?

A

ABL 9q34

BCR 22q11

76
Q

Translocation for AML?

A

(8;21)(q22;q22)

15;17)(q22;q21

77
Q

Translocation for Burkitt lymphoma

A

(8;14)(q24;q32)

78
Q

Translocation for mantle cell lymphoma

A

(11;14)(q13;q32)

79
Q

Translocation for follicular lymphoma

A

(14;18)(q32;q21)

80
Q

What do microRNAs (miRs) do?

A

Mediate sequence-specific inhibition of mRNA translation via RNA-induced silencing complex

81
Q

What do long noncoding RNAs do?

A

Modulate gene expression

82
Q

DNMT3A gene

A

Fxn: DNA methylation
Tumor: AML (20%)

83
Q

MLL1 gene

A

Fxn: histone modification
Tumor: AL in infants (90%)

84
Q

MLL2 gene

A

Fxn: histone modification
Tumor: Follicular lymphoma (90%)

85
Q

CREBBP/EP300

A

Fxn: histone acetylation
Tumor: diffuse large B cell lymphoma (40%)

86
Q

ARID1A

A

Fxn: Nucleosome positioning/chromatin remodeling
Tumor: Ovarian clear cell carcinoma (60%) and endometrial carcinoma (30-40%)

87
Q

SNF5

A

Fxn: Nucleosome positioning/chromatin remodeling
Tumor: malignant rhabdoid tumor (100%)

88
Q

PBRM1

A

Fxn: Nucleosome positioning/chromatin remodeling
Tumor: renal carcinoma (30%)

89
Q

HTLV-1

A
  • T cell leukemia/lymphoma

Encodes Tax protein, which turns on pro-survival pathways (PI3K/AKT, NFKB) leading to polyclonal T cell expansion

90
Q

EBV

A

Burkitt lymphoma, B cell lymphomas in T-cell immunosuppressed pts.
*also nasopharyngeal carcinoma (China/Africa)

91
Q

HBV and HCV

A
  • hepatocellular carcinomas d/t chronic inflammation and hepatocellular injury
92
Q

MCV (Merkel cell polyomarvirus)

A
  • Merkel cell carcinoma (skin cancer)
93
Q

HHV-8

A

Kaposi sarcoma

94
Q

H pylori

A

Gastric adenocarcinoma and MALT lymphomas

95
Q

Cushing syndrome associated cancers

A
  • Small cell carcinoma of lung
  • Pancreatic carcinoma
  • Neural tumors
  • via ACTH
96
Q

SIADH associated cancers

A
  • Small cell carcinoma of lung
  • Intracranial neoplasias
  • via ADH or ANP
97
Q

Hypercalcemia

A
  • Squamous cell carcinoma of lung
  • Breast carcinoma
  • Renal carcinoma
  • Adult T-cell leukemia/lymphoma
  • via PTHRP, TGFa, IL-1
98
Q

Hypoglycemia

A
  • Ovarian carcinoma
  • Fibrosarcoma
  • Mesenchymal sarcomas
  • via insulin
99
Q

Polycythemia

A
  • Renal carcinoma
  • Cerebellar hemangioma
  • Hepatocellular carcinoma
  • via erythropoietin
100
Q

Myasthenia

A
  • Bronchogenic carcinoma
  • Thymic neoplasms
  • Immunologic
101
Q

Acanthosis nigricans

A
  • Gastric carcinoma
  • Lung carcinoma
  • Uterine carcinoma
  • Immunologic/EGF
102
Q

Hypertrophic osteoarthropathy/clubbing of fingers

A
  • Bronchogenic carcinoma
  • Thymic neoplasms
  • Unknown cause
103
Q

DIC

A
  • Acute promyelocytic leukemia
  • Prostate carcinoma
  • tumor factors activating clotting
104
Q

Venous thrombosis

A
  • Pancreatic carcinoma
  • Bronchogenic carcinoma
  • Tumor products (mucins activating clotting)
105
Q

HCG associated cancers

A
  • Trophoblastic tumors, nonseminomatous testicular tumors
106
Q

Calcitonin associated cancers

A
  • Medullary carcinoma of thyroid
107
Q

Catecholamine and metabolites associated cancers

A
  • Pheochromocytoma
108
Q

a-fetoprotein associated cancers

A
  • Liver cell cancer

- Nonseminomatous germ cell tumors of testicle

109
Q

Carcinoembryonic antigen associated cancers

A
  • Carcinomas of colon, pancreas, lung, stomach and heart
110
Q

Prostatic acid phosphatase associated cancers

A
  • Prostate cancer
111
Q

Neuron-specifc enolase associated cancers

A
  • Small cell cancer of lung

- Neuroblastoma

112
Q

Igs associated cancers

A
  • Multiple myeloma and other gammopathies
113
Q

CA-125 mucin associated cancers

A

Ovarian cancer

114
Q

CA-19-9 mucin associated cancers

A

Colon, pancreatic cancers

115
Q

CA-15-3 mucin associated cancers

A

Breast cancer

116
Q

TP53, APC, RAS mutants in stool/serum

A

Colon cancer

117
Q

TP53, RAS mutants in stool/serum

A

Pancreatic cancer

118
Q

TP53, RAS mutants in sputum and serum

A

Lung cancer

119
Q

TP53 mutants in urine

A

Bladder cancer

120
Q

What are tumor markers best used for?

A
  • Detecting recurrences

- lack specificity and sensitivity for early detection

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