Cancer Genetics

Question 1

What is a human karyotype?

Answer 1

It shows all the chromosomes present in an individual after they have been stained and arranged in pairs called homologues.

Question 2

What is the centromere?

Answer 2

The region that separates the two arms.

The arm above the centromere which is shorter, is called the p arm, while the longer arm is the q arm.

Question 3

What is the start codon?

Answer 3

Methionine (AUG)

Question 4

What are the three stop codons?

Answer 4

UAA
UAG
UGA

Question 5

Why is DNA referred to as redundant code?

Answer 5

Most amino acids are coded for by more than one triplet codon.
However, each triplet is linked to only one amino acid.

Question 6

What is meant by germline mutations in cancer?

Answer 6

Germline mutations occur in germ cells (ovum or sperm).
Germline mutations may occur de novo or be inherited from parents’ germ cells.
An example of germline mutations linked to cancer are the ones that occur in cancer susceptibility genes like Rb.

Question 7

What does a pap smear screen for?

Answer 7

Cervical cancer

Question 8

What does a mammogram screen for?

Answer 8

Breast cancer

Question 9

What does the PSA test screen for?

Answer 9

Prostate cancer, used along side biopsy and digital rectal exams.

Question 10

What are focal occult blood tests used to detect?

Answer 10

Invisible amounts of blood in the faeces, a possible sign of several disorders, including colon cancer

Question 11

What are the risk factors for cancer?

Answer 11

Smoking, Low energy UV radiation, High energy atomic radiation, Viruses

Question 12

Name the 5 cancers that are caused by the following 5 viruses:

• Epstein-Barr virus
• HPV
• HBV
• Human T-cell lymphotrophic virus
• KSHV

Answer 12

Epstein-Barr virus - Burkitt’s lymphoma
HPV - cervical cancer
HBV - liver cancer
Human T-cell lymphotrophic virus - adult T-cell leukaemia
Kaposi’s sarcoma-associated herpesvirus: Kaposi’s sarcoma

Question 13

Why does KSHV infection in AIDS patients increase risk of cancer?

Answer 13

Kaposi’s sarcoma is not directly caused by HIV infection.
Instead, HIV causes an immune deficiency that makes people more susceptible to viral infection.
Infection by KSHV then stimulates the development of Kaposi’s sarcoma.

Question 14

What is kaposi’s sarcoma?

Answer 14

Kaposi’s sarcoma is a malignant tumor of blood vessels located in the skin.

Question 15

What type of cancer does Li-Fraumeni syndrome increase the risk of?

Answer 15

Sarcomas, brain, breast and leukaemia.

Question 16

What type of cancer does FAP increase the risk of?

Answer 16

Colon, rectum

Question 17

What type of cancer does Fanconi’s aplastic anaemia increase the risk of?

Answer 17

Leukaemia, liver, skin

Question 18

What is a point mutation?

Answer 18

Single base changes in DNA sequences.

Question 19

What is a missense mutation?

Answer 19

Point mutation that substitutes one nucleotide for another, but leaves the rest of the code intact.
The impact depends on the amino acid that is changed and the resulting protein sequence.
If the change is critical to the protein’s catalytic site or to its folding, damage may be severe.

Question 20

What is a nonsense mutation?

Answer 20

Point mutations that change an amino acid codon to one of the three stop codons, which results in premature termination of the protein.

Question 21

What can cause nonsense mutations?

Answer 21

Single base pair substitutions or frameshift mutations

Question 22

What is the Philadelphia chromosome?

Answer 22

In CML, a translocation occurs between chromosomes 9 and 22 creating the BCR-ABL fusion gene
BCR-ABL produces a tyrosine kinase thought to promote the development of leukaemia.

Question 23

How do mutations in DNA repair genes cause cancer? Give an example.

Answer 23

Mutations in DNA repair genes can lead to a failure in repair, which in turn allows subsequent mutations to accumulate. An example in xeroderma pigmentosum.

Question 24

What does a gene have incomplete penetrance?

Answer 24

When all carriers of a certain dominant allele in a population do not express the trait (same genotypes/different phenotypes)

Question 25

Give an example of incomplete penetrance in cancer.

Answer 25

Germline mutations in mismatch repair genes associated with HNPCC are incompletely penetrant.
So not all individuals who carry these mutations will get colorectal cancer, but the risk increases as individuals age. About 20% of carriers will never develop colorectal cancer.

Question 26

What is Lynch syndrome?

Answer 26

HNPCC is an autosomal dominant genetic condition with a high risk of colon cancer.
The increased risk of cancer is due to inherited mutations in DNA mismatch repair genes.

Question 27

What factors influence penetrance?

Answer 27

Carcinogens, oestrogen, hormonal/reproductive factors, DDR, modifier genes.

Question 28

What is autosomal dominant inheritance?

Answer 28

Most hereditary cancer syndromes are inherited in autosomal dominant fashion.
Dominant inheritance occurs when only one copy of an allele is required for a phenotypic expression. In autosomal dominant inheritance, multiple generations express the phenotype, with no skipped generations (assuming complete penetrance).

Question 29

What are phenocopies?

Answer 29

Cases of sporadic cancer are called phenocopies because their phenotype is similar to that of the affected mutation carriers, but their genotype is different.