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BS3003 Cancer Cell and Molecular Biology > Multistep tumourigenesis > Flashcards

Multistep tumourigenesis Flashcards

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1
Q

How are tumours formed and progress (in 4 basic steps)?

A

Origin of cells within a tumour
Multihit hypothesis
Tumour heterogeneity
Tumour microenvironment

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2
Q

Is cancer a genetic disease?

A

Yes

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3
Q

Cancer results from alterations in what?

A

DNA (mutations)

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4
Q

Alterations in DNA that result in cancer are caused primarily by what?

A

Environmental mutagens

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5
Q

What does the accumulation of mutations with time cause?

A

Carcinogenesis

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6
Q

The genetic changes that occur in cancer cells are responsible for inducing what?

A

The ‘hallmarks of cancer’

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7
Q

What are the two types of genes called that are involved in the development of cancer in humans?

A

Oncogenes and tumour suppressor genes

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8
Q

Are the mutations in oncogenes that cause cancer dominant or recessive?

A

Dominant

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9
Q

Are the mutations in tumour suppressor genes that cause cancer dominant or recessive?

A

Recessive

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10
Q

How many cells could a solid tumour contain when it is first detected?

A

> 10 to the 9

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11
Q

Do tumour cells descend from a single ancestral cell (monoclonal) or do they have multiple origins (polyclonal)?

A

Descend from a single ancestral cell, i.e. monoclonal

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12
Q

What are the three pieces of evidence for cancers being monoclonal?

A

X-inactivation mosaics
Myelomas
Chromosomal rearrangements

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13
Q

Every female is a mixture (mosaic) of what two types of cells?

A

Paternal X inactivated cells (Xp)

Maternal X inactivated cells (Xm)

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14
Q

When does X-inactivation occur?

A

In early foetal development

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15
Q

Is X-inactivation random?

A

Yes

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16
Q

In many patients with CML, cancer cells can be distinguished by the presence of what?

A

The Philadelphia (Ph1) chromosome

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17
Q

How does the Philadelphia (Ph1) chromosome arise?

A

By a translocation between chromosomes 9q and 22q

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18
Q

How many cell divisions are there per human in a lifetime?

A

~E16

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19
Q

What is the mutation rate in humans per gene per cell division?

A

E-6

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20
Q

How many gene mutations occur per human in a lifetime?

A

E10

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21
Q

Is a single mutation in a single cell enough to cause cancer?

A

No

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22
Q

Why is a single mutation in a single cell not enough to cause cancer?

A

Several independent mutations in the lineage of one cell are required for cancer
Mutations need to occur in oncogenes and tumour suppressor genes

23
Q

What are the three pieces of evidence for the multihit hypothesis?

A

Epidemiology
Oncogene cooperation
Tumour progression

24
Q

Why does the epidemiology of cancer support the multihit hypothesis?

A

Because the incidence of cancer increases with age
If only one mutation was required to convert a cell to a cancer cell then most cancers would be independent of age but this is not the case

25
Q

Why does tumour progression fit with the multi-hit hypothesis?

A

Because cancer is an initial mild disorder that gradually evolves into a fully-blown disease

26
Q

What are the steps of tumourigenesis?

A 
Normal
Initiated
Pre-cancer (mild, moderate and severe)
Carcinoma in situ
Cancer
27
Q

Define the breakthrough phase

A

A single cell develops a specific driver-gene mutation and begins to divide abnormally

28
Q

Define the expansion phase

A

A cell develops an additional driver-gene mutation that gives rise to a benign tumour

29
Q

Define the invasive phase

A

A cell develops an additional driver-gene mutation in at least one of the indicated pathways enabling it to invade surrounding tissues

30
Q

What phases occur to get from a single abnormal cell to a metastatic cancer?

A

Breakthrough phase
Expansion phase
Invasive phase

31
Q

What does tumour progression involve successive rounds of?

A

Mutation and natural selection

32
Q

What do cancers arise by a process of?

A

Clonal selection

33
Q

What does the first mutation in a cancer cell give?

A

A slight growth advantage

34
Q

What does the second mutation in a cancer cell allow?

A

Its descendants to grow more uncontrollably

35
Q

What does the third mutation in a cancer cell allow?

A

A cell to outgrow others and form a benign tumour

36
Q

What types of cells are in the tumour microenvironment?

A 
Cancer stem cell (CSC)
Cancer cell (CC)
Immune inflammatory cells (ICs)
Invasive cancer cell
Pericyte (PC)
Endothelial cell (EC)
Cancer-associated fibroblast (CAF)
37
Q

What is tumour development dependent on? Give an example that demonstrates this

A

Dependent on the microenvironment

RSV implanted into chicks gives rise to a tumour; however RSV implanted into chick eggs does not give rise to a tumour

38
Q

What can chronic inflammation promote?

A

Tumour progression

39
Q

Cancers develop as a result of mutations to what types of genes?

A

Proto-oncogenes and tumour suppressor genes

40
Q

Are cancers thought to develop from a single or multiple abnormal cells?

A

A single abnormal cell

41
Q

Define the multihit hypothesis

A

Several independent mutations in the lineage of one cell are required for cancer

42
Q

What is there growing evidence for as cancers evolve?

A

Tumour genetic heterogeneity

43
Q

What is tumour development also dependent on?

A

The microenvironment

44
Q

What is cancer?

A

The uncontrolled growth of cells with the ability to metastasise

45
Q

What types of genes to oncogenes arise from?

A

Proto-oncogenes

46
Q

Why is cancer deemed a genetic disease?

A

It is a problem with the genes, but not necessarily an inherited one

47
Q

Are proto-oncogenes and tumour suppressor genes normal in the cell?

A

Yes, until they acquire mutations

48
Q

Around what percentage of cancers of monoclonal?

A

99%

49
Q

What is a leiomyoma?

A

A form of cancer

50
Q

What is myc?

A

A classic oncogene

51
Q

What are E1A and ras?

A

Oncogenes

52
Q

What is one of the main issues in treating cancer?

A

Tumour heterogeneity

53
Q

Essentially, what is the stroma?

A

All cells surrounding the tumour

54
Q

What can help a tumour to grow?

A

The tumour microenvironment

BS3003 Cancer Cell and Molecular Biology (4 decks)

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