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Principles of Physiopathology > Molecular Biology of Neoplasias > Flashcards

Molecular Biology of Neoplasias Flashcards

1
Q

There is a strong rationale for the implications of ___ in the evolution of cancers

A

genetics

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2
Q

What is the molecular etiology of neoplasia/root of all cancers?

A

Genetic mutation

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3
Q

What is a mutation?

A

Alterations in nuclear DNA sequences (genes)

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4
Q

What happens to most mutations?

A

They are repaired

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5
Q

Which non-repaired genes will give rise to neoplasia?

A

Those that control cell growth, division, and differentiation

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6
Q

What are some types of DNA mutations?

A
  • DNA point mutations
  • Chromosomal translocation
  • Gene amplification
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7
Q

Deletions can occur in…

A
  • entire chromosomes
  • parts of chromosomes
  • specific genes
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8
Q

What are some examples of additions?

A
  • Aberrant chromosome replication: trisomy and aneuploidy
  • Amplifications and repeats
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9
Q

What causes genetic mutation?

A
  • Environmental agents
  • Mutations arising during normal cell metabolism
  • Spontaneous errors in DNA replication and repair
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10
Q

What are some examples of environmental agents/mutagens causing genetic mutation?

A
  • Chemical carcinogens
  • Radiation
  • Dietary carcinogens
  • Tobacco smokes
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11
Q

What is an example of a mutation arising during normal cell metabolism?

A

Free radical-induced mutations

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12
Q

A genetic characteristic of all neoplasms is that it’s a result of ___ genetic damage (acquired or inherited)

A

non-lethal

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13
Q

What are the normal regulatory genes that are principal targets of genetic damage?

A
  • Proto-oncogenes
  • Oncogenes
  • Tumor suppressor genes
  • Genes that regulate DNA repair
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14
Q

Neoplasia is a ___ process

A

multi-step

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15
Q

How many mutations are required to generate cancer?

A

6-12

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16
Q

What is the one-hit hypothesis?

A

One mutation can spoil the whole bunch

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17
Q

When proto-oncogenes are mutated, what can they become?

A

Oncogenes

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18
Q

What are three examples of receptor mutations leading to neoplasia?

A
  • ret: stuck in ON position
  • erb: overexpression mutation
  • Her2/neu: 2 copies of human epidermal receptor
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19
Q

The receptor mutation, Her2/neu is important in what cancer?

A

Breast cancer

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20
Q

What is an example of a G protein mutation leading to neoplasia?

A

ras mutation leaves G protein stuck in ON position

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21
Q

What are some examples of nuclear regulatory protein mutations leading to neoplasia?

A

myc, jun, fos genes when activated, turn on last set of genes which turn on cell division

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22
Q

Oncogenes encode proteins called…

A

onco-proteins (which resemble normal products of proto-oncogenes)

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23
Q

What are proto-oncogenes?

A

Cellular genes that promote normal growth and differentiation

24
Q

Proto-oncogenes may become oncogenic by…

A

viral or other exogenous influences

25
Q

Oncogenes are genes which promote…

A

neoplastic growth

26
Q

Oncogenes are mutations of naturally occurring…

A

proto-oncogenes

27
Q

Oncoproteins do not have…

A

important regulatory functions

28
Q

Oncoprotein production in the transformed cell does not depend on…

A

growth factors or other external signals

29
Q

What are the four classes of oncogenes?

A
  1. Growth factors
  2. Growth factor receptors
  3. Membrane associated signal transduction proteins
  4. Nuclear regulatory proteins
30
Q

Sis encodes for…

A

Platelet Derived Growth Factor

31
Q

Polypeptide growth factors normally stimulate…

A

proliferation of cells

32
Q

Mutations of genes that encode growth factors render protein products oncogenic either by ___ or ___

A

overexpression or increased binding capacity

33
Q

Normal receptor binding by growth factor results in…

A

transient activation of tyrosine kinase activity –> transient second messenger activity

34
Q

How do oncogenic receptors differ from normal growth factor receptors?

A

They are either over-expressed or demonstrate persistent activation of enzyme activity –> continuous mitogenic signals to the cell

35
Q

What is an example of continuous activation mutation of an oncogenic growth factor receptor?

A

ret continuous activation

36
Q

What is an example of overexpression mutation of an oncogenic growth factor receptor?

A

erb overexpression

37
Q

What class of oncogene is the Her2/neu gene leading to breast cancer?

A

Growth factor receptor mutation

38
Q

Ras protein (G protein family) is the most well-studied…

A

membrane associated signal transduction protein

39
Q

10-20% of all human cancers contain ___ mutations

A

ras

40
Q

Ras mutation that contributes to neoplasia is a mutation that…

A

maintains ras protein in an activated state

41
Q

What are nuclear regulatory proteins?

A

Proteins which are localized in the nucleus and which bind to DNA and activate transcription of proto-oncogenes

42
Q

What are three nuclear regulatory proteins that may become oncogenes?

A
  • myc
  • jun
  • fos
43
Q

Tumor suppressor genes are involved in…

A

regulation of cell growth via inhibition

44
Q

Inactivation of tumor suppressor genes that leads to neoplasia involves mutations of…

A

both alleles aka “two-hit” hypothesis
ie. recessive genes

45
Q

Name seven common tumor suppressor genes

A
  • RB
  • P53 (guardian of genome)
  • BRCA1/BRCA2
  • NFx
  • WTx
  • DCC
  • APC
46
Q

Li Fraumeni syndrome is a mutation of which tumor suppressor gene?

A

P53

47
Q

Breast carcinoma is caused by mutation of which tumor suppressor gene?

A

BRCA1/BRCA2

48
Q

What mutation in DCC will cause colon carcinoma?

A

Deletion of DCC in colon carcinoma

49
Q

P53 links cell damage with…

A

DNA repair, cell-cycle arrest, and apoptosis

50
Q

P53 assists in DNA repair by causing… and inducing…

A

causing G1 arrest and inducing DNA repair genes

51
Q

What happens with homozygous loss of p53?

A

DNA damage goes un-repaired

52
Q

What percent of all cancers have p53 gene mutation?

A

75%

53
Q

What type of gene is bcl-2?
Overexpression of bcl-2 is found where?

A

bcl-2 is an anti-apoptotic gene
Overexpression found in malignant lymphoma

54
Q

What type of gene is bax?
Deletion of bax can lead to what?

A

bax is a pro-apoptotic gene
Deletion of bax can lead to malignancy

55
Q

Programmed cell death is dictated by interaction/balance of…

A

anti- and pro-apoptotic gene products

56
Q

What is telemorase?
What happens when somatic cells lack telemorase?

A

Enzyme which prevents chromosome shortening (by adding nucleotides)
Somatic cells lacking telemorase will eventually die

57
Q

Do cancer cells “reactivate” telemorase?

A

Yes

Principles of Physiopathology (36 decks)

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