Mutations and Cancer Flashcards
Germaine mutation
a change in the DNA sequence that can be inherited from either parent
somatic mutation
- a change in the DNA sequence in cells other than sperm or egg
- the mutation is present in the cancer cell and its offspring, but not in the patient’s healthy cells
What are the most common mutations in cancer?
somatic mutations
What precent of cancer cases have a clear hereditary component?
5-10%
What types of changes are required for cancer to develop?
somatic changes
mutations & cancer genes
- cancer genes are causally implicated in oncogenesis
- mutations in cancer genes can occur somatically or can be inherited
- mutations in some cancer genes can be inherited from parents, in which case they are present in every cell of the body
- such people are at a higher risk of developing cancer
- somatic mutations can occur in any of the cells of the body except the germ cells and therefore are not passed on to children
Rb
- a classic tumour suppressor
- binds to a protein called E2F1
E2F1
-initiates the G1/S cell cycle transition
Rb and E2F1
- Rb binds to a protein called E2F1
- When bound to Rb, E2F1 can’t function
HER2/neu
- an oncogene
- a growth factor receptor
How is HER2/neu associated with breast cancer?
- 25-30% of breast cancers over-express HER2/neu
- the over expression of HER2/neu leads to resistance of anti-growth signals
- Herceptin can be used to treat cancer with this mutation as it blocks the receptor and stops the tumour growth
mutagens
-are chemical compounds or forms of radiation (such as ultraviolet (UV) light or X-rays) that cause irreversible and heritable changes (mutations) in the cellular genetic material, deoxyribonucleic acid (DNA)
How do viruses lead to cancer and what is an example?
- insertional mutagenesis
- Human Papilloma virus (HPV) is associated with cervical cancer
How do chemicals lead to cancer and what is an example?
- DNA adducts
- Benzo[a]pyrene can cause lung cancer
How do UV and ionizing radiation cause mutagens?
- single and double strand DNA breaks
- UV and ionizing radiation can cause skin cancer
What is an example of bacteria that can lead to cancer?
Helicobacter Pylori causes mutations that lead to gastric cancer
What is a common gas in Manitoba that has been linked to cancer?
radon gas
ultraviolet radiation
- natural radiation is known to be the primary cause of skin cancer
what is the least common type of skin cancer
malignant melanomas
most common type mutations in skin cancer
thymine dimers
What are UV-light-induced mutations
substitution C>T ot G>A
- lead to the formation of covalent bonds between two adjacent pyridines in the DNA molecule
mutations in BRAF and p53
- mutation in BRAF (oncogene), can lead to aggressive cell growth and therefore the development of malignant melanoma
- a mutation in p53 (tumour suppressor) causes precancerous lesions
tobacco smoke
- contains more than 60 mutagens that bind and chemically modify DNA
- tobacco smoke have carcinogens polycyclic aromatic hydrocarbons like bento[a]pyrene and the nicotine-derived nitrosamines
- these will cause G-T mutations
carcinogens
a exposure that cause mutations in the DNA that is associated with cancer
hyperplasia
growth in the lung
dysplasia
ruptured tissue
KRAS
- is a genetic marker that can be used to screen for cancer
- gene codes for a signalling molecules that regulates the cell cycle
- mutations in KRAS are present in many cancer, including pancreatic and colon cancer
substitution
a nucleotide base is substituted with another base
deletion
a nucleotide base or bases are removed from the sequence
insertion
a set of nucleotide base or bases are added into a sequence
inversion
a set of nucleotide is switched or inverted
duplication
a set of nucleotide in the sequence is repeated
missense mutations
- changes the amino acid
- changes the effect or alters the function of the protein
silent mutations
- do not change the amino acid
- do not change the effect or alter the function of the protein
What are common mutations in KRAS?
amino acid 12, 13, 61, 146
What is the common mutations in KRAS?
- amino acid 12
- important in KRAS binding and recognizes the binding of GTP
KRAS gene
- helps to transmit external growth signals to the cell nucleus driving normal cell growth
- is activated when its binds to GTP
- is inactivated or “switched off” when GTP is hydrolyses to GDP
- if the KRAS is not recognizing the presence of GTP, and doesn’t switch off, then KRAS will be constantly sending the signal for the cell to keep dividing
