DT: Cancer Genes Flashcards
(46 cards)
1
Q
What is a subsitution mutation?
A
- Point mutation
- Replacing DNA base pair with another
- Where? -Coding and Non-coding regions
2
Q
What does point mutations result in?
A
- Amino acid changes > missense mutations
- Premature stop codons> nonsense mutations
- No change > silent mutation
3
Q
Mutations in non-coding regions affect what?
A
- Introns
- Regulatory elements
- > altering gene expression
- > cancer contribution
4
Q
Mutation in protein coding region result in?
A
- Exons
- Change in amino acid sequence
5
Q
Insertion mutations
A
- Additional nucleotide base added into DNA sequence
- Disrupts reading frame in the coding region
- Leads to frameshift mutations
- Forming abnormal proteins
6
Q
Deletion mutations
A
- Removing nucliotide bases in the DNA sequence
- Frameshift mutations
- Results in dysfunctional proteins
7
Q
Duplication mutations
A
- DNA segment mistakenly repeated
- Resulting from extra gene copy/ part of gene
- Overexpression of affected gene
- Contribute to cancer
8
Q
Inversion mutations
A
- DNA segment orientation is reversed within chromosome
- Disrupts gene function and regulation
- Lead to cancer
9
Q
Translocation mutations
A
- Exchange of genetic material between 2 different chromosomes
- Or within chromosome
- > fusion of genes
- > fusion proteins
10
Q
Give example of translocation mutation?
A
- Philadelphia chromosome
- translocation of chromosome 9 and chromosome 22
- Resulting fusion gene= BCR-ABL
11
Q
What is BCR-ABL gene associated with?
A
- Chronic myeloid leukemia (CML)
- Acute myloid leukemia (AML)
12
Q
How does cancer arise?
A
- ALL -mutations
- This disrupts normal regulation
- Affecting cell growth and division
- Leads to uncontrolled cell division (characteristic of cancer)
13
Q
Somatic Mutations
A
Acquired mutations
90-95%
Nor inherited, mutations during a persons lifetime, NOT passed down to offspring
> damage to genes
14
Q
Inherited Mutations
A
- Germline mutations
- Genetic change-> any cells (incl.reproductive cells)
- Passed directly from parent-> offspring
- 5-10% of cancer cells inherited cancer
15
Q
Factors for somatic mutations
A
- Exposure to carcinogens- Tabacco smoke, UV
- Aging
- Random Errors in DNA replication
- > > SPORADIC CANCER common type
16
Q
What are 2 main groups of cancer genes?
A
- Oncogenes
- Tumor suppressor genes
17
Q
What are oncogenes?
A
- Mutated gene (spontaneous event) > cancer development
- Gain of function
- > acquire new function/overactive
- > > cell proliferation> uncontrolled cell growth
18
Q
What are non-mutated gene regions called?
A
- Proto-oncogenes
- > Role in normal cell function
19
Q
Where are oncogenes primarily found?
A
- Somatic tissues
20
Q
Why is it rare for oncogenes to be present in germline tissues?
A
- Severely affect embryonic development
- Lethal
21
Q
What is tumor supressor genes?
A
- Mutated gene
- Loses ability to restrain cell growth and division
- ‘breaks’ cell division
22
Q
How are Tumor sup’ressive’ gene are activated
A
- Recessive
- Require 2 copes of allele
- One copy of inherited
- Second copy is ACQUIRED
- > Cancer development
23
Q
What is familial cancer syndrome?
A
- Allele inherited within families
24
Q
What is the function of tumor supressor gene?
A
- Genome stability
- Prevent uncontrolled growth in damaged and abnormal cells.
- Via apoptosis
25
What happens when tumor supressor genes are mutated?
* Tumor supressor genes are no longer active 'switched off'
* Abnormal cell growth persist
* Cell growth regulation is compromised (no longer functioning)
26
If a copy is inherited what does this mean in terms of cancer development in an individual?
* High susceptibility to cancer if second copy mutated later in life.
27
What is retinoblastoma?
* Rare eye cancer (children)
* Mutation= RB1= Tumor supressor gene
28
29
What is familial adenomatous polyposis (FAP)-APC
* Inherited
* Polyps- colon and rectum
30
Li-Fraumeni syndrome
Mutation- TP53 (tumor supressor gene)
* High risk -> breast cancer, sarcoma, brain tumour
31
Mutated Oncogene act?
Dominantly
32
33
Family cancers linked to oncogenes
* Multiple endocrine neoplasia Type 2 (MENS)
* >multiple endocrine tumours
34
What are the mechanisms that activate oncogenes?
* Amplification
* Translocation
* Point mutation
(PAT-O)
35
What is amplification?
* Oncogene amplified
* >Multiple copies-> genome
36
Can you give example of amplified oncogene?
* Myc oncogene
* > amplified in cancer cells
* >increased expression and cell proliferation
37
What is translocation?
* Oncogene fusing with other genes
38
Give example of translocation?
* BCR-ABL fusion gene
* >chronic myleoid leukemia
* (chromosome 9 and chromosome 22)
39
Give examples of point mutations that activate oncogenes?
* Ras family of genes
* > Krad
* >Nras
* >Hras
>> Colorectal and lung cancer contributions
(kinase pathway always on)
40
What is Hras?
Oncogene
41
42
Where is Hras oncogene activated?
Bladder carcinoma
>promote uncontrollable cells growth
>cancer development
43
# H-Ras
What is the narrowed mutation region?
* Relatively small DNA region
* 350 BP
* Activate H-Ras gene in bladder carcinoma
* Indicated critical genetic changes occurs within soecifc region
44
What did sequencing the H-Ras reveal?
* Point mutation
* Glycine to Valine amino acid change in the H-Ras protein
45
# H-Ras
How did this single point mutation changing glycine to valine affect the function of the H-Ras protein?
Promote uncontrolled cell growth
Contribute development in bladder carcinoma
46
