Cancer Genetics

Question 1

What two ways can people get cancer from?

Answer 1

Environmental and genetic defects.

Question 2

How do tumours arise/form?

Answer 2

Increased cell division and normal apoptosis
Or
Normal cell division and decreased apoptosis.

Question 3

What is the morphology of cancer cells?

Answer 3

Multiple nuclei
Coarse chromatin
Nucleus overtakes cell
Very little cytoplasm

Question 4

Why is cancer regarded as a micro-evolution?

Answer 4

Grows at an advantage when the cells mutations make it better at growing than normal cells.

Question 5

How do mutations give rise to cancers?

Answer 5

They enhance cell proliferation or they destabilize the genome by removing its repair mechanisms
If at any point there is an issue in the repair mechanism or checkpoint in the cell cycle, then the cell won’t enter G0 and a tumour will form.

Question 6

What do cyclins do?

Answer 6

They regulate the cell cycle by binding to cytoplasmic CDKinases and they regulate other genes that control the cell cycle.
Different cyclins regulate different parts of the cycle.

Question 7

What are oncogenes?

Answer 7

genes that produce products that actively promote cell proliferation
They are mutated proto-oncogenes.

Question 8

What are tumor suppressor genes?

Answer 8

genes that produce products that may inhibit cell proliferation.
They regulate cell growth and survival, and promote apoptosis.

Question 9

What are mutator genes?

Answer 9

Genes that produce products that maintain the integrity of the genome.

Question 10

What spontaneous errors in DNA cause mutations?

Answer 10

errors at meiosis during DNA replication or DNA repair or chemical attack on DNA can give rise to mutations

Question 11

What environmental causes give rise to mutations?

Answer 11

Viruses
Ionising radiation
chemical mutagens in food and environment

(but stable genetic changes give rise to polymorphisms and evolutionary advances)

Question 12

What are germline mutations?

Answer 12

A process that produces heritable changes in DNA

Question 13

What are the three types of germline mutations?

Answer 13

Large changes in entire segments of chromosomes
Small changes or point mutations
Inherited mutations like in the BRCA1 and 2 genes

Question 14

How does chemicals and radiation mutagenesis lead to depurination and thus single point mutations?

Answer 14

chemicals react causing the B-N-glycosidic bond between the purine base and the ribose sugar on the nucleotide to be hydrolysed, removing single bases, leading to the other strand adding in a random base.

Question 15

How does chemicals and radiation mutagenesis lead to deamination of bases?

Answer 15

Causes the hydrolysis of Cytosine into Uracil by removing the NH2 group from Cytosine.
C usually pairs with G but if C is replaced with U then it will pair with A on the opposite strand where a G was meant to be.

Question 16

How does chemicals and radiation mutagenesis lead to the formation of pyrimidine dimers leading to melanomas?

Answer 16

Photochemical reactions by UV radiation create molecular lesions from thymine or cytosine creating mismathces. T-T, T-C or C-C on the same strand.

Question 17

True or false?

Human somatic mutations are passed on or inherited from parent to offspring.

Answer 17

False. Human somatic mutations are only passed on from cell to cell. i.e Lung cancer by smoking
Only germline mutations are inherited.

Question 18

What do oncogenes encode for?

Answer 18

Growth factors that promote cell growtrh and cell communication with the environment and with other cells.
Growth receptors too
If mutated, this can lead to cell proliferation

Question 19

The loss of function of tumor suppressor genes lead to what?

Answer 19

Tumors forming or progressing.

Question 20

Give an example of a TSG.

Answer 20

Retinoblastoma which is a rate inherited childhood tumor

Question 21

What is the two-hit hypothesis for tumor suppressor genes?

Answer 21

You need to develop mutations in 2 of the genes in order to develop a tumor. One-hit is sufficient for the familial form of the tumor.

Question 22

What does the RB gene control/ what is its function?

Answer 22

Controls how the cell progresses through the cell cycle by regulating the stages of the cell cycle.

Question 23

If someone has a mutation in their RB gene, what are the 5 possible outcomes/combinations they may have?

Answer 23

(a) Loss of the normal chromosome by mitotic non-dysfunction so they only inherit the mutated form
(b) Loss of the normal chromosome and reduplicate the mutated RB gene
(c) Recombination of the chromosomes so they swap arms, leading to inheriting the mutation and losing the normal allele.
(d) Normal wildtype allele is deleted so they inherit the mutated form
(e) Random pathogenic mutation on the wildtype allele so they inherit 2 mutated RB genes.

Question 24

How is chromosomal loss/abnormalities (that are inherited) monitored and detected?

Answer 24

By using southern blotting, we can detect bands of the marked RB genes on chromosomes. If there is a loss, a band will not be detected.
Sometimes, the markers all appear on southern blots even though the patient has cancer so further genetic testing must be done.

Question 25

What is the small arm and long arm called on a chromosome?

Answer 25

small- p arm

long- q arm

Question 26

What does this nomenclature for human cytogenetics mean? ……….. t(A;B)(p1;q2)

Answer 26

t= a translocation (swapping of chromosomal material)
A;B= will be a number i.e. chromosome 21 and chromosome 6 (21;6)
p1;q2= genetic information moved from p arm to q arm and the numbers are the region on that arm where the genes are located (bands and sub bands)

Question 27

What does the enzyme telomerase do when it is switched on in cancer cells?

Answer 27

It is normally switched off in all somatic cells.
But when it is switched on in cancer cells, it adds back non-templated telomeric DNA sequences onto the ends (telomeres) of chromosomes.
This means, cells can keep proliferating, even with mutations in.

Question 28

Name 3 simple single chromosomal mutations.

Answer 28

Deletion of a gene
Duplication of a gene
Inversion of a gene (flipped upside down)

Question 29

Name 2 chromosomal mutations that occur between chromosomes.

Answer 29

Insertion (inserting genes from 1 chromosome to another)

Translocation (swapping genes between 2 chromosomes)

Question 30

What is the ABL gene and what tumour is it associated with?

Answer 30

A gene involved in cell division, differentiation and adhesion.
Associated with CML - Chronic Myeloid Leukaemia

Question 31

What is the BCR gene and what tumour is it associated with?

Answer 31

A gene involved in activating GTP-binding proteins.

Associated also with CML

Question 32

What happens when the ABL and BCR genes translocate?

Answer 32

Create a fusion gene on what is now called the philadelphia chromosome, causing cells to continuously activate kinases and have dysregulated cell cycles.
Inhibited apoptosis
Genomic instability

Question 33

When fusion genes are understood (i.e ABL-BCR), what is their treatment?

Answer 33

Block the activation of the fusion proteins by Gleevec which stops uncontrolled proliferation.

Question 34

What is Burkitt’s Lymphoma?

Answer 34

Tumor in which there is dysregulatyion of the c-myc gene by SEVERAL chromosomal translocations.
MYC is put under the regulation of IgH promoter