Cancer Genetics Flashcards
What are somatic mutations?
Where there is a genetic defect in a cell within a specific tissue that develops after birth
What are oncogenes? How are they implicated in cancer?
‘On’ switch genes that promote cell growth in G1
Control genes regulate these ‘on’ switches by preventing cell growth after cell division has happened
Mutations in control genes can prevent oncogene from turning off, causing cell proliferation
What are tumour suppressor genes?
‘Off’ switch genes that check whether cell is ready to enter S-phase and so can prevent proliferation
Disruption to what type of gene, other than oncogene or tumour suppressor gene, can cause cancer?
DNA repair genes, because if they are not working they can’t repair mutations so they persist in the cell line
How many copies/alleles of a mutated oncogene need to be present for cancer to develop?
One, because once the ‘on’ switch is on, cell proliferation occurs indefinitely
Outline the Knudson’s Two-Hit Hypothesis
2 copies/alleles of a mutated tumour suppressor gene or DNA repair gene need to be present for cancer to develop
One mutation makes you susceptible because only the other needs to be disrupted
Two mutations lead to cancer
What does the Knudson’s Two-Hit Hypothesis say about when cancer’s develop?
If you have inherited one mutation in a tumour suppressor gene/DNA repair gene, then since only one (not two) more copy needs to become mutated for you to get cancer, the age of onset of your cancer will be earlier
Late 50s compared to early 40s for breast cancer (the latter have familial BRCA1 and 2 genes)
What % of breast cancer is genetic?
5-10%
Chance of developing breast cancer with BRCA1 or 2 mutation?
85%
What type of gene are BRCA1 and 2?
DNA repair genes
What kind of cancers can BRCA1 and 2 mutations cause?
Breast cancer (male and female) Ovarian cancer
In a pedigree, when might you suspect a BRCA1 or 2 mutation?
Lots of breast (sometimes bilateral) and ovarian cancer (sometimes both in one individual)
Male as well as female
<50 age of diagnosis
Dominant inheritance
Jewish ancestry
What are the two ways of breast screening?
Pros and cons of each?
Mammography
- cheaper
- uses radiation
- young women have denser breasts which show up white… the same colour as cancer
MRI screening
- expensive
- more sensitive in younger women
Surgery to reduce risk of breast and ovarian cancer?
Mastectomy and reconstruction for breast cancer
-risk to <10%
Oophorectomy for ovarian cancer
-risk to <2%
Treatment for BRCA1 or 2 carriers?
How good is it and why?
How do they work?
Possible treatment in PARP (poly-ADP ribose polymerase) inhibitors
Symptom free, effective
Cancer cells have a broken BRCA DNA repair pathway, so in order to not apoptose they go down the PARP DNA repair pathway
PARP inhibitors block this pathway as well, so cancer cell stops proliferating and apoptoses
Inheritance of Familial Adenomatous Polyposis and Lynch syndrome?
What do these cause?
Both autosomal dominant
They both cause bowel cancer
Where is the mutation in FAP?
The APC gene
Which mutations cause Lynch syndrome?
MLH1, MSH2, MSH6, PMS2
Inheritance of BRCA1 or 2?
Autosomal dominant
What happens in FAP? Standard treatment?
Predisposition to bowel polyps - tend to develop during teenage years
Cancer is inevitable, usual onset is 20s
Treat surgically with colectomy
What to look out for in pedigree for Lynch syndrome?
Multiple people with bowel cancer <60
One person with bowel cancer <45
People developing cancer twice
Presence of other cancers like endometrial, ovarian, stomach/small intestine
Screening for bowel cancer?
Colonsocopy
Which gene is mutated in Li-Fraumeni Syndrome, and what is it’s function? Inheritance?
P53 - tumour suppressor gene
Autosomal dominant
Li-Fraumeni complications? Management?
Variety of different cancers seen and often childhood cancer
Basically individual very susceptible to developing cancer
Yearly total body MRI - open access to oncologists
Mutation in MENIN causes? And RET? Inheritance?
Multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 2
Autosomal dominant
Compare MEN1 and 2
MEN1 - Pituitary, pancreas and parathyroid tumours (3 Ps) —> usually benign
MEN2 - Medullary thyroid and paraythyroid cancers, as well as phaeochromocytoms —> usually malignant
