Molecular pathology of cancer

Question 1

Types of somatic mutations

Answer 1

Spontaneous

Induced

Question 2

Types of hereditary cancer

Answer 2

Germline mutations

Question 3

Difference between gremlin and somatic mutations

Answer 3

Germline are consitutional and in all cells of body (inc gametes so passed between generations)
Somatic initially in one cell

Question 4

Indicators of gremlin mutations

Answer 4

Bilateral tumours
Young age
Examination findings - macrocephaly etc

Question 5

Increased genetic cancer risk

Answer 5

2+ close relatives with disease
Cancer development less than 50
Blood relative has genetic abnormality

Question 6

Example of oncogene mutations

Answer 6

RET caused by MEN2

Question 7

What is Lynch syndrome?

Answer 7

Autosomal dominant condition contributing to a variety of cancer

Question 8

Amsterdam criteria

Answer 8

3+ relatives with colorectal/endometrail cancer
2+ generations
1 diagnosed less than 50 y/o
First degree relatives of each other

Question 9

Genes FAP

Answer 9

APC

Question 10

Genes breast and ovarian cancer

Answer 10

BRCA1 and 2

Question 11

Gene Li-Fraumeni

Answer 11

TP53

Question 12

Gene MEN2

Answer 12

RET

Question 13

Gene von Hippel-Lindau sundrome

Answer 13

VHL

Question 14

Genes Lynch syndrome

Answer 14

MLH1/2

Question 15

Retinoblastoma

Answer 15

Familial onset - normally before 1 y/o, normally bilateral tumours caused by RB1 mutation

Question 16

MOA retinoblastoma formation

Answer 16

Normally Rb binds to E2F and stops transcription of genes needed for S phase
Stimulation of Ras -> phosphorylation -> Rb releases E2F transcription and this causes mRNA translation and enzyme/protein formation
If Rb mutated, no binding to E2F so constantly stimulate cancer-causing factors

Question 17

What is FAP?

Answer 17

Lots of intestinal adenomatous polyps 
Develop into cancer with time 
Autosomal dominant 
High penetrance 
Gremlin mutation in APC suppressor gene

Question 18

Li Fraumeni syndrome

Answer 18

Autosomal dominant 
Wide variety of cancers caused by TP 53 mutation 
Young age of onset 
No P53 = no repair of damaged cells 
Breast, osteosarcoma, brain tumours etc

Question 19

Risk factors breast cancer

Answer 19

Nulliparity, early menarche, late menopause, first child after 30, oestrogen exposure (HRT)

Question 20

Which cancers does VHL syndrome pre-dispose people to ?

Answer 20

Hemangioblastomas of brain, spinal cord and retina

Autosomal dominant

Question 21

MEN2A

Answer 21

Medullary thyroid cancer, pheochromocytoma, parathyroid adenoma

Question 22

Mutation of MEN

Answer 22

Activation mutations in RET porto-oncogenes (RET =-receptor tyrosine kinase )
Normally GF binds to RET receptor = phosphorylation of kinase pathways = survival
MEN means RET activated without GF for sustained signalling