Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Genetics PMY-3 > Cancer Genetics 1 > Flashcards

Cancer Genetics 1 Flashcards

1
Q

What is cancer?

A

A group of disorders as a result of accumulation of somatic mutations; genetic diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the characteristics/hallmarks of cancers?

A
  • uncontrolled cell division (unregulated cell proliferation)
  • self sufficient in growth signals
  • defective DNA repair
  • immortal (evade apoptosis)
  • capacity to invade surrounding tissues (metastasis)
  • induce angiogenesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the emerging hallmarks of cancer?

A
  • avoiding immune destruction

- Deregulating cellular energetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the enabling characteristics of cancer?

A
  1. Tumor-promoting inflammation

2. Genome instability and mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Explain cancer as a process

A

Cancer is a multi step process that requires multiple mutations

  • Age related incidence of cancer develops from accumulation of several mutagenic events in single
  • cancer results from mutated gene products or abnormally expressed genes
  • mutations affect multiple cellular functions
  • Incidence of most cancers rises exponentially with age
  • Independent and random mutations are necessary for cell to become malignant
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Outline the pathway for colon cancer?

A
  1. Normal colon epithelium + APC (patient between 30-50 years)
  2. Small adenoma +Kras (patient between 40-60 years)
  3. Large adenoma +PI3K Cell cycle/apoptosis genes TGF-B (patient 50-70 years)
  4. Carcinoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Comeback to karyotypes

A

Come back to karyotypes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the clonal origin of cancer cells

A

Clonal origin
-All cancer cells in primary and secondary tumors are clinical

  • Clonal: Originated from a common ancestral cell that accumulated numerous mutations
  • Supporting evidence : reciprocal translocations and X-inactivation demonstrate that cancer cells are clonal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Explain cancer stem cell hypothesis

A

Most cells within tumors do not proliferate

Cancer stem cell hypothesis

  • tumor cells give rise to cancer stem cells that have capacity for self-renewal
  • Stem cells: undifferentiated cells with capacity for self renewal
  • Presence of cancer stem cells (CSCs) explains self-renewal capacity of a tumor

-CSCs divide asymmetrically to form new CSCs and progenitor (dark blue) cells that in turn give rise to differentiated cancer cells (light blue) that form bulk of the tumor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the role of reciprocal translocations play in cancer?

A

Reciprocal translocations are characteristic of many cancers

  • include white blood cell cancers such as leukemia’s and lymphomas
  • Example: chronic myeloid leukemia: reciprocal translocation between chromosome 9 and 22
  • translocation is present in all tumor cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the role of X-inactivation in cancer development?

A

X-chromosome inactivation occurs early in development at rando:

-All cancer cells within a tumor, both primary and metastatic, within one female individual contain the same inactivated X-inactivated chromosome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Cancer can result from…

A
  • increased cell division

- decreased rates of cell death(evasion of apoptosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What happens to cancer cells in interphase?

A

Interphase-interval between mitotic division
-Cell grows (G1 and G2 phases) and replicates it’s DNA (S phase)

  • Cells that stop proliferating enter G0
    • Do not grow or divide but are metabolically active(neurons)

-Cancer cells are unable to enter G0 and cycle continuously

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the cell cycle control and checkpoints?

A
  • G1/S, G2/M and M checkpoints
  • 3 distinct checkpoints where the cell monitors external signals and internal equilibrium
  • Cells decide whether to proceed to the next stage of the cell cycle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the function of the G1/S as a cell cycle checkpoint?

A

Cell monitors size and DNA integrity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the function about the G2/M cell cycle checkpoint?

A

Cell monitors DNA synthesis and damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the function of M checkpoint?

A

Cell monitors spindle formation and attachment to kinetochores

18
Q

How is the cell cycle regulated?

A

Cell cycle is regulated by cyclins and cyclin-dependent kinases(CDKs)

-synthesis and destruction of cyclins occurs during cell cycle

  • change in concentration of cyclins in variou# phases of the cell cycle
    • levels of cyclin D2 increase at the end of G1
    • levels of cyclin B increase at the end of G2 phase
19
Q

How do cyclins interact with checkpoints?

A

Cyclin is abundant before checkpoint

  • After checkpoint, cyclin is rapidly degraded
  • cyclins associate with CDK
  • cyclin D2 regulates that G1/S checkpoint
  • Cyclin B regulates G2/M checkpoint
20
Q

What is the function of cyclin B ?

A

Cyclin B with CDK causes phosphorylation of M phase proteins

  • Cells progresses to M phase
  • Overexpression of cyclins or cyclin dependent kinases (CDKs) may result in excessive cell division
  • Cyclin B and cyclin D1 overexpression is found in many cancer cells
21
Q

Outline the process of cyclin B functioning

A
  1. Cyclin B levels increase in G2
  2. Cyclin B binds to inactivate CDK1
  3. Active CDK1/cyclin B complexes phosphorylate M phase proteins
  4. Cyclin B degraded in late M phase
22
Q

How does signal transduction work?

A

Signal transduction for cell division
-cells in G0 are stimulated to reenter cell cycle by external growth signals (growth factors)

-signal transduction initiates gene expression that propels cell out of G0 and back into cell cycle (cell is stimulated to divide)

Cancer cells often have defects in soil all transduction pathways involving growth factors

-Protooncogenes code for proteins in these signal transduction

23
Q

What are Protooncogenes?

A
  • present in normal cells

- genes whose products promote cell growth and division

24
Q

What do Protooncogenes encode for?

A
  • transcription factors that stimulate expression of other genes
  • signal transduction molecules that stimulate cell division
  • cell cycle regulators that move cell through cell cycle
25
Q

What are the tumor suppressor genes?

A
  • regulate cell-cycle checkpoints and/or initiate process of apoptosis
  • mutation in tumor suppressor genes result in uncontrolled cell division
26
Q

What are DNA repair genes?

A
  • genes code for proteins involved in DNA repair

- Mutations in DNA repair genes increases the risk of cancer

27
Q

What is an oncogene?

A

Mutated or aberrantly expressed proto-oncogene is converted to an oncogene

  • has a gain of function alteration
  • Contributes to development of cancer and increases rate of cell division
  • Only one allele needs to be mutated or misexpressed to contribute to cancer
    • confers a dominant cancer phenotype
28
Q

What is the function of tumor suppressor genes?

A

Regulate cell cycle checkpoints and initiate process of apoptosis

29
Q

What happens due to mutated tumor genes?

A
  • cells are unable to respond to cell-cycle checkpoints or undergo apoptosis
  • this leads to more mutations and development of cancer
  • loss of function mutations
  • Both copies must be lost to result in cancer (recessive at the tumor level)
30
Q

Outline growth factor signal transduction cascade

A
  1. Growth factors (EGF) bind to receptors on cell surface
  2. Growth factor-receptor complex activates intracellular proteins (ras)
  3. Activation of ras results in activation of downstream proteins
  4. Activation of nuclear transcription factors
  5. Result in expression of proteins required for cell division /proliferation
  6. Cell moves from G1(G0) phase to S phase (DNA synthesis /DNA replication)
31
Q

Define Protooncogenes

A
  • Code for proteins involved in growth factor signal transduction cascade(growth factor pathway )
  • Proteins are normally synthesized in small amounts and well regulated
32
Q

What may a mutation of protooncogene to an oncogene result in?

A

May result in:

-Increased expression of the gene- resulting in increased levels of protein synthesis (greater stimulation for cell division)

OR

Altered protein that is not regulated and is constantly active (constitutively active)

33
Q

What is Ras?

A

A GTP binding cytosolic protein

Ras-GTP is the active form - triggers downstream signals for cell division

Ras is inactivated by hydrolysis of GTP to GDP; Ras-GDP is inactive

34
Q

Outline the Ras Proto-oncogene pathway

A
  1. Growth factor binds to cell-surface receptor
  2. Ras transiently exchanges GTP for GDP
  3. Ras sends signals to cascades of activated proteins
  4. Signal transduction proteins activate transcription factors
  5. Activation or repression of gene expression
35
Q

Ras mutations may be

A
  • overexpression of Ras- resulting in overproduction in constant activation of cell division
  • Mutant ras which is constantly active (point mutations ); Generally, mutant ras loses its GTPase activity and is constitutively active
36
Q

Describe ras genes(proto-oncogenes)

A
  • frequently mutated in cancer
  • encode signal transduction molecules associated with cell membrane
  • Regulate cell growth and division
37
Q

What does the abl proto-oncogene function to do?

A
  • abl codes for tyrosine kinase in growth factor pathway

- abl protein is stringently regulated

38
Q

What causes chronic myelogenous leukemia (CML)?

A
  • translocation of ABL gene on chromosome 9 to BCR gene on chromosome 22
  • Philadelphia chromosome
  • abl gene is next to bcr to form a bcr-abl fusion gene
  • transcription and translation of the fusion gene results in synthesis of bcr-abl fusion protein
  • bcr-abl fusion protein has unregulated tyrosine kinase activity and is always active; it sends constant signals to the cell to keep dividing
39
Q

How can CML be treated?

A

Inhibition of bcr-abl fusion protein

  • Imantib mesylate (Gleevec) is an inhibitor of bcr-abl tyrosine kinase
  • Used in treatment of Ph+CML
  • Gleevec binds to and inhibits tyrosine kinase activity
  • As a result, downstream proteins are not phosphorylated and activated (cell division signal is inhibited)
40
Q

How can oncogenes be activated by amplification?

A

Oncogene amplification May be seen in rapidly progressive cancer

-presence of hundreds of copies of an oncogene in cancer cells

  • Oncogene amplification May be present as:
    • double minutes (extrachromosomal fragments of the oncogenes)
    • homogenously staining regions (multiple copies of the oncogene on a chromosome )
  • Amplification results in synthesis of large quantities (overexpression) of oncoprotein and hence an increased stimulation for the cell to divide (uncontrolled cell division )
  • Double minutes or horse indicate impaired DNA repair

Genetics PMY-3 (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions