Embyronal cancer genes

Question 1

What is the risk of developing cancer in your lifetime vs in childhood?

Answer 1

• lifetime 1 in 3
• childhood 1 in 600
• second most common cause of childhoos death after accidents

Question 2

What kind of cells do adult cancers come from vs childhood cancers?

Answer 2

• adult cancers come usually from epithelial cells and cause carninomas
• childhood cancers come from embyronal cells and cause embyronal cancers

Question 3

What are 3 distinct differences between adult and childhood cancers?

Answer 3

genetic predisposition and oncogene involvement is seen in both - just the number of genetic steps is different similar genes are involved especially in late stage tumours such as p53

Question 4

What are chromosome translocations and what can they lead to?

Answer 4

• chromosome breakage and exchange of genetic material
• proto-oncogene activation by placing strong promoters/enhancers nearby
• fusion proteins can be formed

Question 5

What are some examples of childhood cancers that involve fusion proteins?

Answer 5

• very common in leukaemia e.g. PML-RARA in APML
• can also be in soloid tumours
• Ewing bone tumours have translocations resulting in fusion proteins that favour tumour cell expansion
• Desmoplastic small round cell tumours have fusion proteins involving the WT1 gene that make it tumour promoting

Question 6

How can fusion proteins be used in cancer diagnosis?

Answer 6

• specific fusion proteins seen in certain cancers
• can act as markers and measured by PCR

Question 7

What is retinoblastoma?

Answer 7

• eye tumour
• 40% heriditary with early onset and multiple tumours
• 60% sporadic with one tumour in one eye
• Rb is the classical TSG

Question 8

How does Knudson’s 2-hit theory differ between sporadic and hereditary cancers?

Answer 8

in hereditary cancers the first hit is already present and germline so only one further somatic mutation is required

Question 9

What is RB1?

Answer 9

• tumour suppressor gene that regulates teh G1/S transition
• pushes for terminal differentiation and mutations can lead to stem cell depletion, tumour formation
• always mutated in retinoblastoma
• CMT lectures

Question 10

Give 3 examples of epigenetic alterations that may be seen in embryonal cancers

Answer 10

• tumour suppressor gene hypermethyatlion
• long-range epigenetic silencing (colon cancer)
• loss of imprinting (e.g. IGF2/H19)