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Genetics > Cancer Genetics > Flashcards

Cancer Genetics Flashcards

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1
Q

What factors can cause cancer?

A

Environmental: Chemicals and radiation
Endogenous: Viruses can introduce their genes
Genetics: Alterations in genes, increase susceptibility can be passed on

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2
Q

What differentiates benign and malignant tumors?

A

Benign cells are well-differentiated lacks ability to invade and metastasise. Malignant are poorly differentiated and capable of metastasis.

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3
Q

What are microscopic characteristics of Cancers? (7)

A 
Large number of dividing cells
Large, variably shapes nucleus
Large nucleus cytoplasm ratio
Variation in size and shape
Loss of normal cell features
Disorganised arrangement
Poorly defined tumor boundary
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4
Q

What is the link in the Gene expression of nuclearporins in advanced prostrate cancer?

A

APC ( tumor suppressor gene by controlling beta-cotinine levels)

Nuclear pore increase = influx of beta-cotinine

Beta-cotinine is a transcription F which is often mutated in cancer.

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5
Q

What are the differences between Carcinomas and Sarcomas?

A

Carcinoma : cells covering external/internal body surfaces ( lung, breast, colon - epithelial cancers)

Sarcoma : cells found in supporting tissues ( bone, cartilage, fat, connective tissue, muscle )

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6
Q

Why do children has higher rates of ALL, AML, Germ cell, Brain cancers?

A

Higher risk of cancer in the tissues undergoing higher rate of proliferation

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7
Q

What are the 6 hallmarks of cancer?

A

( These override the anti-cancer defence in cells )

  • Self sufficiency in growth signals
  • Insensitivity to anti-growth signals
  • Tissue invasion and metastasis
  • Limitless replicative potential
  • Sustained angiogenesis
  • Evading apoptosis
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8
Q

What are germ-line mutations?

A

Mutation in egg or sperm which leads to all cells being affected in offspring.

These are hence heritable

Rare cancers ( 10% )

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9
Q

Why are Somatic mutation cancers ‘genetic’ but ‘non-heritable?

A

Genetic because they occur through gene events affected by environment etc

Cannot be passed on to offspring

( 90% of cancers )

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10
Q

How are cancer germ-line mutations identified?

A

Positional cloning linkage studies

gene mapping followed by gene identification.

Once chromosome region identified and sequenced, can compare with normal population

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11
Q

Which Gene is usually mutated in hereditary breast ovarian cancer syndrome

A

BRCA 1 gene

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12
Q

What types of genetic mutations may occur?

A 
Deletions
Duplications
Inversions
Translocation
Single base substitutions
Chromosome instability
Aneuploidy
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13
Q

Which types of genes are usually mutated?

Provide a example

A

Oncogenes, Tumour suppressor genes, DNA repair genes

Colon cancer can begin with APC defect (tumor suppressor gene) = cell proliferation

Proliferation = more mutations e.g. repair genes, growth related genes (K-ras)

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14
Q

What are some emerging cancer hallmarks and cancer enabling characteristics?

A
  • Avoiding immune destruction
  • Deregulating cellular energetics
  • Genome instability mutation
  • Tumor promoting inflammation
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15
Q

What is the mutational signature of UV light damage?

A

C to T transition

Formation of a covalent bond between two adjacent pyridimes ( C and T ) creating a dimer

If these changes happen in certain genes it can cause malignant malenoma

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16
Q

What is the mutational signature of smoking causing lung cancer?

A

G to T transitions become prevalent

17
Q

What are passenger mutations?

A

Mutations that don’t contribute to development of cancer but have occurred during growth of cancer. Driver mutations can come subsequently.

18
Q

What are driver mutations?

A

Contribute to cancer development, provide a selective growth advantage so will lead to clonal expansion

19
Q

What are Oncogenes?

A

1 mutation at high level can cause cancer

Dominant, gain-of-function mutation by driver mutations

Most acquired not inherited mutations

20
Q

How can Driver mutations be distinguished from passenger mutations?

A

By comparing risk of cancer from the normal rate of background mutations from various genes to a sample in which a certain gene is mutating more frequently and is linked to a higher risk of cancer.

Or

Driver mutations tend to have a greater impact on protein function than passenger mutations do.

21
Q

Example of an acquired oncogene mutation which causes a cancer?

A

Chromosome rearrangement leading to BCR-ABL gene formation

Leads to CML

22
Q

How can an mutated Ras protein lead to cancer?

A

Once switched on the protein causes a signalling pathway switches on other proteins and inevitably genes linked to cell cancer enabling hallmarks.

23
Q

Example of Multiple endocrine neoplasia type 2 (MEN2) as an inherited mutation of an oncogene?

A

Mutation in RET gene

People with this syndrome can develop medullary cancer of thyroid

24
Q

What do the following inherited oncogene mutations cause?

KIT gene
MET gene
CDK4 gene

A

GISTs
Hereditary papillary renal cancer
Malignant melanoma

25
Q

Why are most loss-of-function mutations in tumour suppressor genes recessive?

A

2-Hit hypothesis:
Both alleles that code for a protein must be affected for affect to be manifested

1st event : inherited mutation
2nd event : loss of good copy somatically

Leads to cancer

26
Q

What does the 2 Hit hypothesis mean in relation to germ-line or somatic cell mutations?

A

Because in germ-line mutations every cell already has an affected copy. Chances of getting a 2nd somatic mutation is higher. Than a somatic cell getting mutations to both its loss-of-function genes.

27
Q

What does TP53 gene damage lead to?

A

Reduces p53 which is a tumour suppressor gene and regulates the cell cycle

28
Q

In what two ways can the TP53 gene be damaged?

A

Li-Fraumeni syndrome : inherit one functional copy of TP53 and so will be likely to develop tumours early

By mutagens

29
Q

What are BRCA1/BRCA2 examples of?

A

DNA repair genes : code for proteins to repair errors during cell DNA replication before the cell divides.

30
Q

What can mutations in DNA repair genes lead to? (3)

A

Cell with DNA damage will either:

  • dormancy
  • apoptosis
  • cell divisions leading to mutation accumulation and cancer
31
Q

How can viruses affect cell behaviour?

A

DNA damage by inserting their genomes

Cell regulation disruption ( can increase rate of growth )

Altered versions of genes they may have picked up from previous hosts can be inserted

32
Q

What are three examples of cancers associated with viruses?

A

Cervical cancer : Papillomavirus
Liver cancer : hepatitis virus
Burkitt’s Lymphoma : Epstein-Barr virus

Stomach cancer : H Pylori
Ovarian cancer : HPV

33
Q

How can we identify cancer susceptibility genes in a population?

A

Genome wide association studies

Genetics (6 decks)

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