Cancer in families and individuals Flashcards
What is the difference between somatic and germline mutation?
Somatic - occurs in BODY cells, so cannot be passed to offspring
Germline - mutation in GAMETES - meaning it can be passed to offspring
Recall the types of mutation
Aneuploidy - loss or gain of single chromosome
Point - missense, nonsense
Frameshift - insertion, deletion - macro
How do mutations cause cancer
The accumulation of nonsense mutations leads to truncated proteins, which cannot function correctly.
These proteins change pathways that are responsible for cell cycles. Thus, there is disorder.
What are the hallmarks of cancer?
Dysregulated growth
Apoptosis evasion
Limitless replication
Metastasis
Genome instability and mutation
What three disorders do genome instability lead to?
Growth
- angiogenesis
- control of growth signals
Death
- apoptosis evasion
- limitless replication
Behaviour
- Metastasis
- Promotion of inflammation
What are the two classes of cancer causing genes?
Oncogenes
Tumour-suppressor genes
How do oncogenes cause cancer?
Faulty and over-expressed, so activate and amplify cell cycle
Growth and transcription factors are OVER-expressed
- Promote growth and proliferation in cells
How do tumour suppressor genes cause cancer?
Lead to early cessation of cell cycle
Normally control apoptosis and DNA repair, but are DELETED or mutated, leading to faulty cell division as NO LONGER controlling
What s the difference in a passenger and driver mutation
Passenger - mutation that occurs during cancer but doesn’t contribute to it
Driver - mutation that contributes to cancer development
Why is inactivation of TS gene on one allele not enough to cause cancer?
One allele hit reduces level of protein, little phenotypic effect
BOth alleles leads to total loss of transcription of TS gene, meaning cell cycle continues to go badly.
Why might someone who has a disposition to a cancer not obtain it?
Need a somatic mutation too, maybe
How do mutations in BRCA 1 & 2 influence risk of ovarian and breast cancer?
2-4pc of breast cancer caused by this, and 60pc of people who have germline are at risk of cancer, earlier onset htan those w/out germline component
First hit is GERMLINE
Second is SOMATIC deletion
BRCA required for DNA repair, so mutation results in development of cancer
Which two colorectal diseases occur as a result of defected cell division?
Familial adenomatous polyposis
- characterised by polyp growth
- due to mutation in APC gene - cell division
Lynch syndrome (HNPCC)
- Mutation in MLH gene - DNA repair
- 80pc cancer risk
HOw are inherited-cancer patients managed?
Screening
Counselling
Chemo
How might a translocation lead to cancer?
The newly formed fusion gene by have oncogenic properties
