Molecular basis of cancer

Question 1

Types of mutation

Answer 1

Point mutations
-change in amino acid
-frameshift
-introduce STOP codon
-change splicing
Gene amplifications
Chromosomal translocations

Question 2

Characteristics of cancer cells

Answer 2

Excess proliferation without external stimuli
Loss of control mechanisms
Loss of apoptosis
Defects in DNA
Irreversible, limitless change
Acquisition of blood supply - angiogenesis
-invasion of surrounding structures

Question 3

What do cancer cells always have?

Answer 3

Mutations in genes

Question 4

Mutations in DNA can lead to changes in levels or function of gene product

Answer 4

In one base happen all the time and leads to

• can change sequence of mRNA
• this can change tRNA but often won’t
• this can change amino acid, but probably not

Question 5

Frameshift

Answer 5

Point mutation, one base chopped out (e.g. by sunlight)
Causes a big problem
Changing every tRNA, because all bases afterwards are shifted along

Question 6

Amplification

Answer 6

Entire section of chromosome, or duplication of chromosomes

e.g. Her2 becomes overexpressed if amplified, so cell divides much more than it should

Question 7

Chromosomal translocation

Answer 7

Happens in fertilisation and development but should not neo-natally
E.g. chrosome 9 and 22 swap a bit
-fusion protein with tyrosine kinase activity so transcribed a lot more
-Philadephia chromosome

Question 8

Somatic mutation

Answer 8

Occur in nongermline tissues

Nonheritable

Question 9

Germline mutations

Answer 9

Present in egg or sperm
Are heritable
Cause cancer family syndrome
Can not affect the person who originally gets mutation but child could be affected

Question 10

Dark matter of cell

Answer 10

Most RNA does not encode protein, nor is it directly involved in protein synthesis
Non-coding RNA
-miRNA
-IncRNA
-antisense
A lot of this has functions! So not just protein coding that causes cancer

Question 11

Causes of somatic mutations

Answer 11

Diabetes

Lung cancer

Question 12

Genes involved in cancer

Answer 12

Oncogenes
Tumour suppressor genes
Apoptosis genes
Mismatch repair genes
-these groups overlap a lot

Question 13

Oncogenes

Answer 13

Give signal to divide (G1)
Accelerator for cell proliferation
Promote autonomous cell growth and proliferation
> expression (activation) in malignancy

Question 14

Tumour suppressor genes

Answer 14

Tell cell to stop dividing (S)
Brake to cell prolliferation
Loss of expression (gene deletion) or function (mutations) in malignancy

Question 15

DNA repair genes

Answer 15

Recognise mutations within DNA and repair them

After S

Question 16

What do oncogenes code for?

Answer 16

Growth factor and their receptors, signal transducers and cell cycle components

Question 17

Normal function of oncogenes

Answer 17

Proto-oncogenes

Normal function in controlling cell proliferation and cell division

Question 18

What do tumour suppressor genes code for?

Answer 18

Code for factors which control cell cycle, regulate apoptosis, transcription or cell interactions

Question 19

Normal function of tumour suppressor genes

Answer 19

Suppressing cell proliferation and maintaining tissue integrity

Question 20

Two hit hypothesis

Answer 20

Hit 1: inherited loss of gene on one chromosome +
Hit 2: sporadic loss on second chromosome
–> cancer

Question 21

Two hit hypothesis examples

Answer 21

Retinoblastoma

Question 22

Apoptosis genes

Answer 22

Genes that regulate normal cell death. May see
> activity of gene which inhibits apoptosis
< activity of genes which promote apoptosis
BCL-2 overexpressed in lymphomas

Question 23

Mismatch repair genes

Answer 23

Code for enzymes important for repair of damaged DNA
-DNA damage common due to environmental carcinogens
Loss of expression (deletion) or function (mutation) in malignancy
> risk of mutations & activation or loss of oncogenes & tumour suppressor genes

Question 24

Factors in carcinogens

Answer 24

Genetic e.g. somatic
Environmental e.g. sunlight
Chemicals e.g. nitrosamines (tobacco)
Viruses e.g. HPV

Question 25

Multistage carcinogens

Answer 25

Normal cell –> activation of oncogenes/ supression of TSG/ faults in DNA repair –> precancer –> multiple genetic events –> cancer

Question 26

Bowel carcinogenesis

Answer 26

Normal –> hyperplasia –> adenoma –> Carcinoma –> metastasis

Question 27

Oral cancer carcinogenesis

Answer 27

Normal –> patch –> field –> aneuploid –> tumour –> metastasis

Question 28

Epigenetics

Answer 28

-chemical changes to DNA
-often occur because of environmental factors, age etc.
-increasingly thought to be important in cancer
E.g. methylation in wrong place

Question 29

The tumour microenvironment

Answer 29

First stops tumour

Then can corrupt and spread it