Tumour Pathology 5 Flashcards

1
Q

What influences disorders of cell growth?

A
  • Tumour suppressor genes
  • Inherited factors in carcinogenesis
  • Oncogenes
  • Viral carcinogenesis
  • Precursors of cancer
  • Multistep process of tumour development
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2
Q

What influences carcinogenesis?

A
  • Geographic and environmental factors
  • Age
  • Hereditary
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3
Q

What are proto-oncogenes?

A

-Normal genes that promote normal cell growth and mitosis

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4
Q

What are tumour suppressor genes?

A

Normal growth inhibiting genes

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5
Q

What do tumour suppressor genes include?

A
  • Genes negatively regulating mitosis-Rb
  • Genes regulating apoptosis
  • Genes regulating DNA repair
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6
Q

What usually happen to tumour suppressor genes before a normal cell transforms into a cancer cell?

A

A series of several mutations

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7
Q

What is a key event in tumour formation?

A

Uncontrolled cell proliferation via cell cycle dysregulation via loss of tumour suppressor gene function

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8
Q

What is the retinoblastoma gene?

A

An anti-oncogene

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9
Q

What do Rb gene mutations favour?

A

Cell proliferation

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10
Q

What mimics the effect of pRb loss?

A

Mutations in other genes controlling pRb phosphorylation

  • Mutational activation of cyclin D or CDK4
  • Mutational inactivation of CDKIs also drive proliferation
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11
Q

What releases the cell cycle brake?

A

Absent or inactive pRb

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12
Q

What has to happen to tumour suppressor genes for cancer to arise?

A

There must be loss/inactivation of both normal allelic copies

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13
Q

Describe the 2 hit hypothesis in the inherited and sporadic forms of anti-oncogenes such as Rb.

A
Inherited form
-One defective inherited copy of pRb
-Somatic point mutation of other copy
Sporadic form
-Both hits occur in a single cell
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14
Q

What chromosome contains the defective inherited copy of pRb?

A

13q14

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15
Q

How can carcinogenesis be hereditary?

A
  • Inherited cancer syndromes
  • Familial cancers
  • Autosomal recessive syndromes of defective DNA repair
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16
Q

Describe inheritance of cancer syndromes?

A
  • Strong family history of uncommon site-specific cancers

- Autosomal dominant inheritance of a single mutant gene

17
Q

Give examples of inherited cancer syndromes?

A
  • Familial retinoblastoma
  • Familial adenomatous polyposis of colon
  • Multiple endocrine neoplasia
  • Neurofibromatosis
  • Von Hippel-Lindau syndrome
18
Q

Describe familial cancers.

A
  • Family clustering of cancers but individual predisposition unclear
  • Multifactorial inheritance
  • Early age of onset
  • Multiple/bilateral tumours
19
Q

Give examples of familial cancers.

A
  • Some breast cancers
  • Some ovarian cancers
  • Non-FAP colon cancers
20
Q

What are oncogenes?

A

Cancer causing genes derived from proto-oncogenes

21
Q

How are oncogenes activated?

A

Alteration of proto-oncogene structure
-Point mutation
-Chromosome rearrangements and translocations
Dysregulation of proto-oncogene expression
-Gene amplification
-Overexpression

22
Q

What do oncogenes generate?

A

Active oncoprotein products

23
Q

Give examples of active oncoprotein products.

A
  • Growth factors
  • Growth factor receptors
  • Proteins involved in signal transduction
  • Nuclear regulatory proteins
  • Cell cycle regulators
24
Q

What are 2 exampled of cancer which can arise as a result of overexpression of oncogenes?

A
  • Burkitt lymphoma: C-myc moves close to IgH gene

- Mantle cell lymphoma: cyclin D1 gene to IgH

25
Q

Give an example of a cancer that results due to recombination to form chimeric proteins.

A

Chronic myeloid leukaemia

26
Q

What DNA viruses are known to cause cancer in humans?

A
  • HPV (cervical cancer)
  • Hepatitis B (liver cancer)
  • EBV (Burkitt lymphoma)
27
Q

What are the different mechanisms or viral carcinogenesis?

A
  • Virus genome inserts near a host proto-oncogene
  • Viral promoter or other transcription regulation elements cause proto-oncogene over-expression
  • Retroviruses insert an oncogene into host DNA causing cell division
28
Q

What is a DNA adduct?

A

A chemical carcinogen or their active metabolite which reacts to form covalently bound products

29
Q

How does chemical carcinogenesis work?

A

DNA adduct formation at particular chromosome sites lead to activation of oncogenes and suppression of anti-oncogenes

30
Q

Why is carcinogenesis considered a multistep process?

A
  • All sporadic cancers harbour multiple genetic aberrations
  • Abnormalities accumulate with time
  • Activation of several oncogenes and loss of 2 or more anti-oncogenes occurs in most cancers
31
Q

What are the key regulators in cancer?

A
  • p16
  • cyclin D
  • CDK4
  • Rb
  • In the majority of cancers these are mutated