Tumour Suppressor Genes and Clinical Implications Flashcards
In what proportion of cancers is p53 mutated?
p53 is mutated in 50% of cancers.
What is the Knudson 2 hit hypothesis?
The Knudson 2 hit hypothesis states that tumor suppressor genes require both alleles to be inactivated in order to cause cancer.
With which cancer is the APC tumour suppressor gene associated?
APC is associated with colorectal cancer.
With which cancers are BRCA1 and 2 tumour suppressor genes associated?
- BRCA1 is associated with both breast and ovarian cancers.
- BRCA2 is associated with breast cancer.
With which cancer is the DPC4 tumour suppressor gene associated?
DPC4 is associated with pancreatic cancer.
With which cancer is the INK4 tumour suppressor gene associated?
INK4 is associated with:
1 - Melanoma.
2 - Lung carcinoma.
3 - Brain tumours.
4 - Leukaemias.
5 - Lymphomas.
With which cancer is the MADR2 tumour suppressor gene associated?
MADR2 is associated with colorectal cancer.
With which cancer is the NF1 tumour suppressor gene associated?
NF1 is associated with neurofibrosarcoma.
With which cancer is the NF2 tumour suppressor gene associated?
NF2 is associated with meningioma.
With which cancer is the p53 tumour suppressor gene associated?
Remember brain tumours, but p53 is associated with loads of cancers so cba ennit just write down every cancer you can think of.
With which cancer is the PTC tumour suppressor gene associated?
PTC is associated with basal cell carcinoma.
With which cancer is the PTEN tumour suppressor gene associated?
PTEN is associated with loads of cancers so cba ennit just write down every cancer you can think of.
With which cancer is the Rb tumour suppressor gene associated?
Rb is associated with:
1 - Retinoblastoma.
2 - Sarcomas.
3 - Bladder cancer.
4 - Breast cancer.
5 - Lung carcinoma.
With which cancer is the VHL tumour suppressor gene associated?
VHL is associated with renal cell carcinoma.
With which cancer is the WT1 tumour suppressor gene associated?
WT1 is associated with Wilms tumour (a type of kidney cancer).
What type of genetic change most commonly underlies thyroid cancer?
Which signalling pathway is most commonly affected in thyroid cancer?
- Thyroid cancer is most commonly caused by dysregulation of oncogenes rather than dysregulation of tumour suppressor genes.
- Uncontrolled activation of the MAPK (ras/raf/mek/erk) pathway occurs in most thyroid cancers.
How do BRAF mutations affect thyroid cancer progression?
BRAF mutations increase the risk of:
1 - Extrathyroidal invasion.
2 - Lymph node metastases.
Define anaplastic.
A tumour is anaplastic if it has significantly differentiated from, and has therefore lost the morphological characteristics of, the tissue from which it originates.
How do p53 mutations affect thyroid cancer progression?
p53 mutations trigger anaplasia of thyroid cancers.
What is Cowden’s syndrome?
What causes it?
- Cowden’s syndrome is an autosomal dominant disorder that increases the risk of developing various cancers.
- It is caused by a germline mutation in p10, a tumour suppressor gene.
What is familial adenomatous polyposis?
What causes it?
- Familial adenomatous polyposis is an autosomal dominant condition that increases the risk of developing colorectal cancer.
- It is caused by a biallelic mutation in the MYH gene, a tumour suppressor gene which encodes a glycosylase (remember these are involved in DNA repair).
Describe the differences between the pathogenesis of colon cancers that occur on the left side and the right side of the colon.
- Left sided colon cancers are often caused by a loss of heterozygosity (aneuploidy or polyploidy), resulting in loss of APC function.
- Right sided colon cancers are often caused by microsatellite instabilities, resulting in mutation of beta catenin.
List 5 genes that can contribute to melanoma formation in order of frequency (from highest to lowest).
Are these genes oncogenes or tumour suppressor genes?
1 - BRAF (an oncogene).
2 - NRAS (an oncogene).
3 - PTEN (a tumour suppressor).
4 - NF1 (a tumour suppressor).
5 - CKIT (an oncogene).
List the cell signalling pathways that are affected in melanoma.
Pathways affected in melanoma include:
1 - The MAPK (ras/raf/mek/erk) pathway.
2 - The PI3K/AKT pathway.
