GEN: Genetics of cancer

Question 1

what percentage of the human genome are genes?

Answer 1

1.5% -proteins, non-coding RNA

Question 2

what percentage of the human genome are related sequences?

Answer 2

40% -introns, transcriptional reg. regions

Question 3

what percentage of the human genome is repetitive DNA?

Answer 3

45% -centromeres,telomeres,interspersed repeats, mini/micro satellites

Question 4

what 3 things can cause DNA damage?

Answer 4

• DNA replication errors in cell division
• UV/ionising radiation
• reactive oxygen species

Question 5

what are somatic mutations?

Answer 5

DNA damage within a cell

Question 6

what can somatic mutations cause

Answer 6

• cell death
• damage to non-coding DNA
• damage gene controlling cell growth
• inactive tumour suppressor gene
• active an oncogene
• create new fusion gene

Question 7

what are tumours?

Answer 7

clonal expansions of genetically abnormal cells

Question 8

what are 2 targeted therapies?

Answer 8

• bevacizumab - binds to VEGF reducing blood vessel formation
• imantinib - blocks tyrosine kinase activity

Question 9

what 3 genes are associated with cancer predisposition?

Answer 9

tumour suppressor gene
- important for cell growth rate controlling, if bi-allelic loss/mutation = sporadic cancer

oncogene
- accelerate cell division, cancer arises when stuck in on mode

DNA damage-response/repair genes
- constantly repairing DNA, cancer arises due to accumulation of mutations across genome - BRCA1/BRCA2

Question 10

what are 3 DNA repair mechanisms?

Answer 10

• mismatch repair -if insufficient, lynch syndrome ⇒ colon, ovarian, endometrial cancer
• double strand break repair - BRCA1/2
• nucleotide excision repair - XP

Question 11

when are most cancer susceptibility genes dominant?

Answer 11

incomplete penetrance - “skip” generations where individuals inherit altered cancer susceptibility genes (not cancer)

Question 12

what are the main features of cancer?

Answer 12

• young onset
• multiple primary cancers in same person
• same type of cancer in several relatives
• recognisable pattern of cancer in family

Question 13

what are the two types of genetic mutations?

Answer 13

1. somatic
2. germline (constitutional)

Question 14

what type of genetic mutations do most cancers carry?

Answer 14

somatic mutations not present in gremlin ⇒no inherited susceptibility for developing cancer

Question 15

what are the two types of genetic tests?

Answer 15

1. diagnostic - full screen gene (affected patient)
2. predictive - specific mutation targeting that has been identified in another fam member (unaffected patient)

Question 16

what is the incidence for lynch syndrome?

Answer 16

1 in 250

Question 17

what does lynch syndrome result from?

Answer 17

mismatch repair deficiency

Question 18

what does NICE recommend for lynch syndrome testing?

Answer 18

immunohistochemistry to identify tumours with MMR deficiency

Question 19

what are the mismatch repair genes?

Answer 19

• MLH1
• MSH2
• MSH6
• PMS2

Question 20

what is familial adenomatous polyposis FAP

Answer 20

autosomal dominant condition, 100% penetrant with polyps throughout colon

Question 21

what do BRCA1/2 do?

Answer 21

repair double stranded DNA breaks

Question 22

what is Li-Fraumeni syndrome?

Answer 22

rare high risk cancer disease caused by mutations of TP53

Question 23

what is Peutz-Jehgers syndrome?

Answer 23

autosomal dominant

caused by mutations in STK11 gene

cancer predisposition

Question 24

what is Cowden syndrome?

Answer 24

mutation of PTEN gene, developmental delay