Lecture 2

Question 1

How are oncogenes activated?

Answer 1

G- genetic mutations
C- chromosomal translocation
G- gene amplification
E - epigenetic factors
I - increased protein stability

Question 2

How do oncogenes contribute to cancer?

Answer 2

They help cells avoid apoptosis. They increase cell growth, increase cell motility, invasion and loss of differentiation

Question 3

Oncogenes are activated versions of

Answer 3

normal cellular genes (proto-oncogenes).

Question 4

Conversion of proto-oncogenes to oncogenes

Answer 4

Point mutation: Constitutively active or increased activity
Gene amplification: Normal protein overproduced
Chromosome rearrangement: Nearness to strong enhancer leads to increased protein expression

Question 5

Initial discovery of point mutations

Answer 5

: DNA
sequence analysis revealed a
point mutation in the H-ras
gene in a bladder carcinoma
This mutational event led
to a glycine>valine change in
the H-Ras protein.
* This led to a change in the
structure of H-Ras and
affected the functioning of
H-Ras>leading to
constitutive Ras activity.
* Ras is located downstream
of many growth factor
signalling pathways
including HER2 & EGFR

Question 6

Point mutations in what genes are common events in multiple cancers?

Answer 6

Point Mutations
in H-RAS, K-RAS
and N-RAS genes

Question 7

All Ras oncoproteins (H-, K- or N-Ras) were found to be mutated

Answer 7

codons 12, 13 and 61 in various cancer
types.

Question 8

Gene Amplification
what is amplified in some breast cancers which often
leads to increased expression levels of the

Answer 8

HER2 and HER 2 protein

Question 9

FISH (fluorescence in situ hybridization) analysis using a
fluorescence-labelled DNA probe was used to detect the

Answer 9

erbB2/HER2 or the CCND1/cyclin D1 gene (figure opposite).
When used to analyse nuclei of normal diploid cells these
probes would generate 2 spots.

Question 10

What plays a key role in the cell division cycle

Answer 10

Cyclin D1

Question 11

Chromosomal translocation:
Burkitt’s lymphoma, a B cell cancer common in Africa where malaria and Epstein-Barr Virus (EBV) infection are cofactors.
In Burkitt’s lymphoma, 3 alternative reciprocal chromosomal translocations are found involving the Ig heavy or light chain
gene loci on chromosomes

Answer 11

14 (IgH), 2 and 22 and chromosome 8. The c-myc gene is located on chromosome 8q24 and as a
result of these translocation events the c-myc gene is placed under the control of one of three highly active transcriptional
regulators. This leads to overproduced normal c-myc because the strong Ig promoter can upregulate the adjacent c-myc
gene.

Question 12

Are tumors the result of a change in
DNA sequence?

Answer 12

Usually
Broadly cancers arise due to Genetic (DNA sequence) or
Epigenetic (eg hypermethylation of p16 and p15 genes in
acute leukemia) alterations in 3 types of genes:
Oncogenes, Tumour Suppressor Genes and Caretaker
Genes (such as DNA repair genes)

Question 13

What is the evidence that tumours are the result of a change in DNA seq?

Answer 13

1. Cells in a tumor generally share the same DNA abnormalities
2. Correlation between mutagenesis (initiate changes in DNA
   sequence) and carcinogenesis