Genetics 4 - Cancer Flashcards
What are the hallmarks of cancer?
- Disregulated growth
- Evasion of apoptosis
- Limitless replication
- Metastisis
- IMPORTANT: genome instability and mutation
Why is cancer a polyclonal disease?
Cumulative changes result in cancer, meaning that there are many different cells with different mutations in one tumour.
What are driver mutations in cancer?
An initial mutation that occurs in either oncogenes or tumour supressor genes. This first hit is usually a point mutation which cant produce a phenotypic effect.
Summarise the two hit hypothesis.
Hit 1 is a point mutation, which reduces protein level but doesnt cause phenotypic effect. Therefore, inactivation of a second allele is required - this is hit 2, causes total loss of transcription.
This is required in tumour suppressor genes.
What is the function of proto-oncogenes? Give some examples.
They promote growth and proliferation, overriding apoptosis:
- Growth factors
- Transcription factors
- Tyrosine kinases
What is the function of tumour suppressors?
These regulate cell division at the DNA damage checkpoints. They can cause apoptosis and DNA repair.
How can cancers be identified in the genetics?
They can be identified by a loss of heterogenity due to mutations.
What is the difference between familial retinoblastoma and a sporadic retinoblastoma?
Familial - first hit is inherited, second hit is a somatic mutation
Sporadic - two somatic mutations occur in the same cell (hit 1 & hit 2)
What inherited mutation is linked to breast and ovarian cancer?
Germline mutations in BRCA1 and BRCA2, DNA repair genes. They give rise to a 60% risk of cancer by age 90. BRCA2 mutations also predispose risk of breast cancer in men.
What two diseases result in an inherited predisposition to colorectal cancer?
- Familial adenomatous polyposis (FAP)
- Lynch syndrome (HNPCC)
What are the colorectal cancer risks in patients with familial adenomatous polyposis?
Almost a 100% lifetime risk of cancer.
Responsible for >1% of colorectal cancers.
What is the risk of colorectal cancer in patients with lynch syndrome?
Responsible for 3% of cancer cases, and 90% of familial cases.
The lifetime risk for cancer is around 80%.
How are patients treated if a inherited cancer syndrome is detected?
- If a patient has positive family history then they will recieve genetic screening/counseling.
- If they are mutation positive then they recieve surveillance, chemoprevention and family work-up
How may the causes of polygenic cancer be studied?
- Using genome wide association studies to look for SNPs.
- Using transcriptome chips/mRNA arrays to identify differently expressed transcripts (compares expression between malignant and normal tissue)
What are cytogenetic changes in cancer?
These are visible changes in chromosome structure or number, which accumulate during disease progression. (Eg. Fusion genes, macroduplications or macrodeletions, aneuploidy)
