What is cancer?

Question 1

What is cancer?

Answer 1

uncontrolled growth of abnormal cells in a tissue, invasive and metastasising (seeded to other parts of the body)
A metastasised cancer is more challenging to treat and can only be treated systemically

Question 2

What is the origin of cancers?

Answer 2

tumours arise from normal tissues

• can arise form nearly all specialised cell types throughout the body
• different tissues have diff combos of genes being transcribed
• even within the same tissue, diff combo of genes are transcribed at different stages of differentiation

Question 3

What cell type do the majority of cancers arise from?

Answer 3

epithelial cells - mostly exposed to external environment e.g. GIT and lungs

Question 4

What are carcinomas?

Answer 4

Squamous cell carcinoma=lining epithelial cells - most common
Adenocarcinoma=secreting epithelium

Question 5

Other than carcinomas, what other cancer types are there?

Answer 5

Sarcomas=from mesenchymal cells

Leukaemias= from haemoatopoietic tissue and cells of immune system -lymphoid and myeloid tumours

Question 6

What types of tumours do children appear to be more susceptible to?

Answer 6

Brain tumours (gliomas and neuroblastomas) and lymphocytic leukaemia

Question 7

What do tumours look like?

Answer 7

material tends to look undifferentiated

cells in the lumen look disorientated which could be hyperplasia (not yet a tumour)

Question 8

What does metaplasia mean?

Answer 8

Change from on differentiated form to another

Question 9

What does neoplasia mean?

Answer 9

Doesn’t mean cancer, it just means excess growth

Question 10

What are polyps?

Answer 10

pre-invasive adenomas- greater chance of developing as we age

Question 11

What are the basic causes of cancer?

Answer 11

A genetic disorder at the cellular level

• chromosomes are altered in most types
• radiation can disrupt chromosomal structure leading to the cell dying

Question 12

What happens in T cell prolymphocytic leukaemia?

Answer 12

chromosome translocations - cell survives and proliferates
- single translocation was the initial change but then more genetic changes occur over years causing damage to nearly all T-cells

Question 13

What is an oncogene?

Answer 13

Positive regulator of cell growth - makes cell grow

even when only one allele is mutated

Question 14

What happens when replicative immortality is activated?

Answer 14

circumvention of senescence and crisis

increased expression and activity of telomerase= an enzyme which keeps cell out of senescence

Question 15

What type of disorder is cancer and what happens?

Answer 15

it is a genetic disorder of monoclonal growth- damage occurs in one cell initially and then this further proliferates (progeny of that one original cell)
- NO such thing as a polyclonal tumour

An individual or even an individual tissue can have multiple tumours but it is very rare and each tumour is monoclonal

Question 16

When you stain a tumour with G6PD what do you expect to see?

Answer 16

expect the staining to be exactly the same in each cell of the tumour

Question 17

Where can mutations occur?

Answer 17

in germline cells - inherit a mutation which predisposes you to a tumour
in somatic cells - vast majority are within these types of cells and in the elderly

Question 18

What are some examples of tumour suppressor genes and oncogenes mutated in germline cells and some conditions associated with germline mutations?

Answer 18

TSG= Rb gene, BRCA1
Oncogene=H-ras
Costello syndrome, Rhabdomyosarcoma, ganglioneurolastoma

Question 19

What are some examples of tumour suppressor genes and oncogenes mutated in somatic cells?

Answer 19

TSG= Rb again, APC 
Oncogene= cMyc, c-Abl

Question 20

A defective RB1 gene causes?

Answer 20

Familial retinoblastoma

Question 21

A defective TP53 gene causes?

Answer 21

Li-Fraumeni

Question 22

A defective APC gene causes?

Answer 22

Familial adenomatous polyposis coli

Question 23

Defective MLH1, MSH2, MSH6, PMS1 or PMS2 genes can cause?

Answer 23

Hereditary non-polyposis colorectal cancer

Question 24

What happens if you inherit a mutant Rb allele?

Answer 24

Familial inheritance - doesn’t be you have retinoblastoma because you need both alleles to be mutated but because you’ve already inherited one mutant allele you are at increased risk of developing retinoblastoma

Whereas in sporadic retinoblastoma, you would need to lose the function of both Rb alleles in the same cell to develop the condition

Question 25

What are tumour suppressor genes?

Answer 25

they are negative regulators of cell growth - you need to lose both alleles to lose suppressor effect

Question 26

What different types of genes may initiate cancer?

Answer 26

• Genes that normally control growth
• Genes that control passing on of signals from outside the cell (receptors) across the cytoplasm to the nucleus
• genes involved in apoptosis
• genes involved in the cell cycle
• genes that produce stem cells
• genes involved in the integrity of genome repair

Question 27

How do mutations arise?

Answer 27

Copying errors during DNA replication - largest source of mutation
Spontaneous depurination
Exposure to different agents -e.g. UV light, tobacco products

Question 28

What are the different types of mutations?

Answer 28

Nonsense mutations

• normal codon replaced by termination codon to give rise to truncated protein
• may occur by substitution or by frameshift

Missense mutation

• single amino acid change
• may or may not have an affect on the protein function
• may give rise to a partial or complete loss of function

Question 29

What is the progressive development of cancer?

Answer 29

multiple genetic steps that occur over years

- normal cell to early adenoma to late adenoma to carcinoma

Question 30

What is the vogelstein model?

Answer 30

Model for colorectal cancer

1. normal epithelium
2. hydroprolieferative epithelium
3. adenoma class 1 <1cm
4. adenoma class 2 >1cm
5. adenoma class 3 - large adenoma foci of carcinoma
6. carcinoma which can go on to metastasise

Question 31

What are the hallmarks of cancer?

Answer 31

• self-sufficiency in growth signals
• insensitivity to growth inhibitor signals
• evasion of apoptosis
• limitless replicative potential
• tissue invasion and metastasis
• sustained angiogenesis
• genetic diversity and inflammation
• reprogramming of energy metabolism
• evading immune destruction
• tumour microenvironment