Genetics Wk 8

Front 1

What is cancer?

Back 1

When abnormal cells divide without control and spread to other tissues

Front 2

What is metastasis?

Back 2

Describes what happens when cells from a malignant neoplasm break away from the primary tumor and travel through the blood/lymph systems and form neoplasms at distant sites

Front 3

What is a sarcoma?

Back 3

CA which arises in mesenchymal tissue (bone, CT, muscle, CNS)

Front 4

What is a carcinoma?

Back 4

CA which originates in epithelial tissue

Front 5

What is myeloid tissue?

Back 5

Red bone marrow

Front 6

What characterizes hereditary CA syndrome?

Back 6

1. Site specific
2. Early onset
3. Bilateral

Front 7

What is an oncogene?

Back 7

It is a mutant allele of a proto-oncogene

Front 8

What is a proto-oncogene?

Back 8

Normal protein coding genes that promote the growth and survival of cells; when they mutate, they can stimulate cell proliferation or inhibit apoptosis.

Front 9

What sorts of proteins do proto-oncogenes encode for?

Back 9

Proteins involved in:
1. Signaling pathways for cell-proliferation
2. Transcription factors controlling the expression of growth-promoting genes
3. Inhibitors of the apoptotic process

Front 10

What are tumor suppressing genes?

Back 10

They protect a cell from moving towards becoming cancerous

Front 11

How do TSGs work?

Back 11

1. Repressing genes essential for the continuation of the cell cycle
2. Coupling the cell-cycle to DNA damage
3. DNA repair
4. Cell death
5. Metastasis suppression

Front 12

What are the two main classifications of TSGs?

Back 12

1. Gatekeepers
2. Caretakers

Front 13

What do gatekeeper TSGs do?

Back 13

1. Control cell growth
2. Block tumor development by regulating transition of cell through gates in cell cycle
3. Promote apoptosis if things aren't going right

Front 14

What do caretaker TSGs do?

Back 14

1. Protect the integrity of the genome

Front 15

What happens with mutant caretaker TSGs?

Back 15

They permit mutations to accumulate in oncogenes and gatekeeper TSGs, which can then lead to CA

Front 16

What do caretaker TSGs code for?

Back 16

Proteins which:
-Detect/repair mutations
-Possibly those involved in the apoptosis process

Front 17

How are tumors initiated?

Back 17

1. Mutations in the gene/propmoter region that turn one allele of a proto-oncogene into an oncogene
2. Heterochronic mutations
3. Chromosomal translocations (w/non-homologous chromosomes)
4. Loss of fxn of both alleles or a dominant negative mutation of one allele of a TSG

Front 18

How do tumors progress?

Back 18

A cancer progresses by accumulating additional genetic damage.

Front 19

How does genetic errors accumulate?

Back 19

-By mutations in or epigenetic silencing of, the caretaker genes that encode for repairing damaged DNA
-Altered expression of genes that promote vascularization and spread of the tumor through local invasion and metastasis

Front 20

How does the environment act in cancer?

Back 20

Certain agents can act as mutagens that cause somatic mutations, which then cause cancer formation

Front 21

What are the two classes of chemical carcinogens?

Back 21

1. Direct-acting: bind to DNA and cause mutations
2. Pro-carcinogens: converted metabolically to active carcinogens

Front 22

Are oncogenes dominant or recessive?

Back 22

Dominant

Front 23

When are oncogenes not a result of a mutation in DNA?

Back 23

When the mutation is the result of translocation; a mutation in the chromosome

Front 24

How is an oncogene activated?

Back 24

-Gain of function mutation in the gene
-Mutation in the regulatory elements of the gene
-Increase in the copy number of the proto-oncogene, leading to unregulated heterochronic or ectopic expression

Front 25

How many oncogenic chromosome transolcations have been found?

Back 25

Over 40

Front 26

What happens when there is a translocation between chromosomes 9 and 22?

Back 26

Philadelphia chromosome translocation: causes chronic myelogenous leukemia

Front 27

What is telomerase?

Back 27

It is a reverse transcriptase that is required to synthesize the hexamer repeat (TTAGGG) at the end of chromosomes

Front 28

How does a telomerase mutation cause CA?

Back 28

If telomeres aren't shortened as cells age, then they never stop growing/dividing

Front 29

Why do both alleles of a TSG need to be mutated?

Back 29

Because a normal allele can rescue the mutant

Front 30

What is hereditary retinoblastoma?

Back 30

-Disease affecting both eyes; usu onset in early childhood

Front 31

What is non-hereditary retinoblastoma?

Back 31

A sporadic CA that occurs in one eye later in childhood

Front 32

What is the two hit mutation model?

Back 32

One allele can be inherited in a damaged form; then a somatic mutation in the normal allele can cause a loss of fxn mutation to both alleles, resulting in CA

Front 33

What do BRCA1 AND BRCA2 code for?

Back 33

Nuclear proteins in the same multi-protein complex

Front 34

What does BRCA1 do?

Back 34

Helps repair damaged DNA or destroy cells which cannot be repaired

Front 35

What does BRCA2 do?

Back 35

Repair of chromosomal damage w/ an important role in the error-free repair of DNA double strand breaks

Front 36

What do mutations in BRCA1 usually come from?

Back 36

Base pair replacements or DNA rearrangements

Front 37

What do mutations in BRCA2 come from?

Back 37

Usually insertions or deletions of a small number of DNA BPs in the gene

Front 38

What is p53?

Back 38

it regulates the cell cycle and fxns as a tumor suppressor; it is thought to be involved in preventing CA

Front 39

What is TP53?

Back 39

The gene that codes for p53

Front 40

Where are mutations of TP53 seen?

Back 40

IN CA of the breast, ovaries, bladder, and cervix

Front 41

Where is the RB1 gene implicated in?

Back 41

Breast CA

Front 42

What is LOH?

Back 42

It is the loss of normal fxn of one allele of a gene in which the other allele was already inactivated

Front 43

What are some causes of LOH?

Back 43

1. Chromosome loss
2. Deletion
3. Unbalanced translocation
4. Loss and reduplication
5. Meiotic recombination

Front 44

Is LOH a feature in both heritable and sporadic tumors?

Back 44

Yes

Front 45

What is Li-Fraumeni Syndrome?

Back 45

Disorder that greatly increases the chances of developing cancer

Front 46

What is unusual about LFS ppls?

Back 46

They have one of the two mutations needed to inactivate TP53 in their germline

Front 47

What are the 2 classes of tumor viruses?

Back 47

1. DNA tumor virus
2. RNA tumor virus

Front 48

What do the two classes of tumor viruses have in common?

Back 48

The ability to integrate their own genome into that of the host cell

Front 49

What is odd about HBV?

Back 49

Its DNA is transcribed into RNA and then the RNA is converted back to DNA; reverse transcription

Front 50

Which retroviruses cause CA?

Back 50

Only those which contain oncogenes (v-oncs)