Pathology - Final - Molecular Biology Of Cancer

Front 1

This gene is associated with pancreatic carcinoma

Back 1

K-ras

Front 2

These oncogenes are growth factors

Back 2

v-sis

Front 3

These oncogenes are growth factor receptors

Back 3

ret
c-kit
EGF-R
HER2-neu

Front 4

These oncogenes are signal transduction proteins

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Ras
raf
src
MDM2

Front 5

These oncogenes are nuclear regulatory factors

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N-myc (neuroblastoma and gliablastoma)
L-myc (small cell lung carcinoma)

Front 6

These oncogenes are cell cycle proteins

Back 6

Cyclins
CDKs

Front 7

These are tumor suppressor genes

Back 7

Transcription factors (p53, WT-1)
Cell-cycle inhibitors (Rb, CDKIs)
Signal transduction molecules (APC, beta-catenin, neurofibromin)
Cell surface receptors (TGF-beta receptor)
DNA repair proteins (ATM, p53)
Genes that promote apoptosis

Front 8

These genes are involved in angiogenesis

Back 8

VEGF
bFGF
Angiostatin
Endostatin
Antithrombin II
TSP-2

Front 9

These genes are involved in invasion and metastasis

Back 9

Cadherin and catenins
MMPs, collagenases and TIMPs
Integrins

Front 10

T/F: Oncogenes rarely arise from genes encoding growth factors

Back 10

True.

Front 11

This gene is normally expressed in neuroendocrine cells such as parafollicular C cells of the thyroid, adrenal medulla and parathyroid cells.

Back 11

ret

Front 12

This gene is associated with MEN types 2A and 2B, and familial medullary thyroid carcinoma

Back 12

ret

Front 13

This gene is associated with GI stromal tumors

Back 13

c-kit

Front 14

These oncogenes are ligand-dependant, showing increased ligand sensitivity and receptor hyperactivity

Back 14

EGF-R genes (c-erbB1, c-erbB2)

Front 15

Point mutations of this gene are the single most common abnormality in human tumors.

Back 15

Ras

Front 16

15-20% of human tumors contain mutated version of this protein

Back 16

Ras

Front 17

These types of cancers are characterized by persistent expression or overexpression of nuclear regulatory factors

Back 17

Neuroblastoma and glioblastoma
Small cell lung cancer

Front 18

This describes the activation of proto-oncogenes, and these are ways by which it can occur

Back 18

Gain of function, which can be caused by:
(1) Point mutations
(2) Deletions (changes in structure)
(3) DNA amplification

Front 19

This describes the activation of tumor suppressor genes

Back 19

Loss of heterozygosity

Front 20

This oncoprotein is a G-protein

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Ras

Front 21

This oncoprotein normally functions by activating the MAP kinase pathway, which targets nuclear transcription factors that can signal apoptosis, proliferation and other cell activities

Back 21

Ras

Front 22

Mutations of this oncogene lead to its diminished GTP-ase activity, thus the protein is constitutively active since it cannot unbind GTP

Back 22

Ras

Front 23

This gene is amplified in many soft tissue carcinomas

Back 23

MDM2, a p53 antagonist

Front 24

These oncogenes are sometimes activated by DNA amplification

Back 24

N-myc (in 25% of neuroblastomas) and HER2-neu

Front 25

Oncogenes of hematopoietic tumors and soft tissue sarcomas are frequently activated by this mechanism

Back 25

Chromosomal translocation (eg, Philadelphia chromosome in CML, Ig promoter in Burkitt's lymphoma)

Front 26

Two ways in which chromosomal arrangement can activate oncogenes

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(1) Proto-oncogenes coupled with a new promoter (c-myc in Burkitt's lymphoma--Ig heavy chain promoter)
(2) Creation of chimeric proteins (eg, bcr-abl product in CML)

Front 27

This protein has increased tyrosine kinase activity and abnormal cellular localization

Back 27

bcr-abl, the fusion protein product of Ph

Front 28

Familial Retinoblastoma

Back 28

Model for the role of tumor suppressor genes in carcinogenesis. Associated with the Rb gene. Note that although the gene is a recessive oncogene, the disease is autosomomal dominant since only one copy of the gene is necessary to induce the condition.

Front 29

These are mechanisms of loss of heterozygosity (LOH)

Back 29

(1) Homologous or other recombination event during mitosis
(2) Nondisjunction at mitosis resulting in deletion of wt allele
(3) Epigenetics (eg, methylation)
* Point mutations are NOT likely because they are usually repaired

Front 30

This TSG is regulated by Cyclin D
CDK complexes, which inactive it by phosphorylation

Back 30

Rb

Front 31

In its (unphosphorylated) activated state, Rb binds this protein and thereby inhibits the cell cycle

Back 31

E2F, a transcription factor for proteins involved in DNS replication (G1->S transition)

Front 32

p21

Back 32

A CDK inhibitor (part of the Kip-Cip family) that is activated by p53 in response to DNA damage, inducing cell cycle arrest

Front 33

Loss of this gene causes increased mutation frequencies and genomic instability

Back 33

p53

Front 34

This TSG is inactivated in 50% of cancers

Back 34

p53

Front 35

Unlike most TSGs, mutations of this TSG can be "dominant" because it causes dimerization of other wt gene products

Back 35

p53

Front 36

These are two ways in which p53 can be transformed

Back 36

(1) Loss of p53
(2) Overexpression of MDM2, a p53 inhibitor

Front 37

DNA viruses that cause cancer usually do so by this mechanism

Back 37

They knock out TSGs by binding and inactivating them

Front 38

Retroviruses that cause cancer usually do so by this mechanism

Back 38

They carry transgenes that act as oncogenes, which are inserted into the host genome

Front 39

HPV E6

Back 39

HPV protein that binds p53

Front 40

HPV E7

Back 40

HPV protein that binds Rb

Front 41

Inactivation of these genes leads to a specific tissue distribution of cancer

Back 41

"Gatekeeper" TSGs (APC, NF1, Rb, VHL)

Front 42

This gene can act as both a "gatekeeper" and a "caretaker" gene

Back 42

p53

Front 43

Microsatellites

Back 43

Tandem repeats of 1-6 DNA bases. These are examined to detect replicative errors (RER), since they are more likely to contract or expand if DNA repair machinery is damaged

Front 44

These genes are highly (50-85%) associated with lifetime risk of breast and ovarian cancer in women

Back 44

BRCA1, BRCA2. These are DNA repair enzymes

Front 45

This gene defect is associated with 80% of follicular lymphomas

Back 45

Inhibition of apoptosis by overexpression of bcl-2

Front 46

T/F: Inactivation of bcl-2 could possibly help cure cancer

Back 46

True. Bcl-2 block apoptosis, thus inactivating it would induce death of the cancer cells.

Front 47

These cancers tend to be more curable

Back 47

Cancers with normal p53 (eg, hematopoietic and germ cell tumors)

Front 48

Hayflick index

Back 48

Normal cells can only divide 50-60 times, after which telomeric erosion is detected and the cell goes into senescence (G0 state)

Front 49

These mutations may cause cells to proliferate beyond the Hayflick index

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p53, Rb pathway mutations

Front 50

Telomerase

Back 50

Ribonucleoprotein complex that reconstructrs telomeres. Germ cell and stem cell protein. Expressed in 85-90% of "immortal" cells

Front 51

Angiogenic switch

Back 51

Balance between angiogenesis inducers and angiogenesis inhibitors.

Front 52

This is an endothelial cell mitogen and motogen that stimulates the formation of new blood vessels

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VEGF

Front 53

This protein is upregulated by hypoxia and is elevated near areas of tumor necrosis

Back 53

VEGF

Front 54

This protein inhibits VEGF

Back 54

von Hippel Landau (VHL)

Front 55

This protein negatively regulates a serious of hypoxia-inducible genes

Back 55

VHL

Front 56

This TSG works in part by inhibiting angiogenesis

Back 56

VHL

Front 57

p53 works as a TSG in part by inhibiting this process

Back 57

Angiogenesis

Front 58

This is the percentage of cancer patients who will have clinically detectable metastases at the time of initial dx

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30%

Front 59

T/F: Circulating tumor cells can be detected in the circulation of patients who do NOT develop overt metastatic disease

Back 59

True.

Front 60

These are all the steps that must go right in order for invasion and metastasis to occur

Back 60

1. Detachment and decreased cellular adhesion (cadherins)
2. Matrix degradation (MMPs, TIMPs, collagenases)
3. Cell-matrix attachments (integrins)
4. Angiogenesis
5. Motility and migration (GFs, matrix molecules, cytokines)
6. Vascular extravasation (attachment to endothelium)
7. Avoidance of immune surveillance
8. Survival and proliferation in new environment

Front 61

These are transmembrane glycoproteins that mediate homotypic cell-cell interactions at adherens junctions

Back 61

Cadherins

Front 62

These function as tumor suppressors or metastasis suppressor proteins

Back 62

Cadherins

Front 63

Reduced expression of this protein leads to increased degredation on the part of tumor cells

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TIMPs (tissue inhibitors of metalloproteinases)

Front 64

These are transmembrane receptors for BM and ECM components that regulate apoptosis, proliferation, motility and differentiation. They are also responsible for adhesion to vascular BMs.

Back 64

Integrins

Front 65

Integrin switching

Back 65

Results in decreased adhesion to BMs and increased adhesiveness and migration over alternative ECM components--this is the basis for anchorage-independent growth.

Front 66

Motility of tumor cells is stimulated by these two things

Back 66

1. Growth factors
2. ECM and ECM fragments (vitro- & fibronectin, laminin, type I collagen)

Front 67

These are methods by which tumor cells may avoid detection by the immune system

Back 67

1. Cloaking of tumor-specific Ags
2. Inactivation of leukocytes

Front 68

Breast and prostate cancers have a predilection for metastasizing to this site

Back 68

Bone

Front 69

These are possible ways to target metastasis therapeutically

Back 69

1. anti-adhesive agents
2. anti-invasive agents
3. anti-motility agents

Front 70

5-azacytidine

Back 70

Inhibitor of DNA methylation--possible therapeutic value in reversing epigenetic changes to the genome (eg, hypomethylation of oncogenes, hypermethylation of TSGs)

Front 71

Herceptin

Back 71

Monoclonal antibody targeting c-erbB2. Licensed for use in metastatic breast cancer, but only effective in cancers overexpressing erbB2 (Her-2neu)

Front 72

Mylotarg (Gemtuzumab)

Back 72

Cytotoxic monoclonal antibody to CD33 (overexpressed on AML cells)

Front 73

Zevalin (Y-ibritumomab tiuxetan)

Back 73

Cytotoxic monoclonal antibody to CD20. The first radioimmuno-therapeutic agent to be tested in clinical trials

Front 74

Gleevec

Back 74

Tyrosine kinase inhibitor. Used to treat CML. Developed by Brian Druker at OHSU

Front 75

ATRA

Back 75

All-transretinoic acid. Used in acute promyelocytic leukemia (APML) to restore RAR-alpha-mediated differentation of tumor cells