Genetic predisposition to cancer IA %% +

Question 1

Cancer genetics

Answer 1

• ‘Cancer is a genetic disease of somatic cells’ (all body cells except reproductive ones)
• Most cancers happen by ‘chance’ or due to environmental factors
• A small proportion of cancers happen because of an increased inherited predisposition to cancer

Question 2

Cancer from gene mutations

Answer 2

Somatic mutations

• Occur in nongermline tissues
• Are nonheritable

Germ line mutations

• Present in egg or sperm
• Are heritable
• Cause cancer family syndromes

Question 3

Oncogenes

Answer 3

• Proto-oncogenes – normal gene that codes for proteins to regulate cell growth and differentiation.
• Mutations can change a proto-oncogene into an oncogene
• Oncogenes can accelerate cell division
• Cancer arises when stuck in “on” mode

Question 4

Tumour suppressor genes

Answer 4

• The cell’s brakes for cell growth
• TS Genes inhibit cell cycle or promote apoptosis or both
• Cancer arises when both brakes fail

Question 5

2-hit hypothesis (pic)

Answer 5

Question 6

DNA damage response genes

Answer 6

• The repair mechanics for DNA
• Cancer arises when both damage response genes fail, speeding the accumulation of mutations in other critical genes

Question 7

Microsatellite instability (MSI)

Answer 7

• MMR (mismatch repair) corrects errors that spontaneously occur during DNA replication like single base mismatches or short insertions and deletions
• MSI is the phenotypic evidence that MMR is not functioning normally.
• Cells with abnormally functioning MMR tend to accumulate errors.
• Novel Microsatellite fragments (simple sequence repeats - SSRs) are created

Question 8

Dysplastic definition

Answer 8

• Dysplastic – ‘benign’ but could progress to malignancy.
• Cells show abnormalities of appearance & cell maturation. Sometimes referred to as ‘pre-malignant’.

Question 9

De Novo Mutations

Answer 9

• New (de novo) mutation occurs in germ cell of parent
• No family history of hereditary cancer syndrome

Question 10

Most Cancer Susceptibility Genes Are Dominant With Incomplete Penetrance

Answer 10

• Penetrance is often incomplete
• May appear to “skip” generations
• Individuals inherit altered cancer susceptibility gene,not cancer

Question 11

BRCA1 & 2 functions

Answer 11

BRCA1

• Checkpoint mediator
• DNA damage signalling and repair
• Chromatin remodelling (inactive X chromosome)
• Transcription (not essential for this)

BRCA2

• DNA repair by HR (homologous recombination)